ClinVar Genomic variation as it relates to human health
NM_001715.3(BLK):c.211G>A (p.Ala71Thr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001715.3(BLK):c.211G>A (p.Ala71Thr)
Variation ID: 12319 Accession: VCV000012319.38
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p23.1 8: 11548067 (GRCh38) [ NCBI UCSC ] 8: 11405576 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 May 12, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001715.3:c.211G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001706.2:p.Ala71Thr missense NM_001330465.2:c.-3G>A 5 prime UTR NC_000008.11:g.11548067G>A NC_000008.10:g.11405576G>A NG_023543.2:g.59056G>A P51451:p.Ala71Thr - Protein change
- A71T
- Other names
- -
- Canonical SPDI
- NC_000008.11:11548066:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.01238 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.01156
Exome Aggregation Consortium (ExAC) 0.01171
1000 Genomes Project 0.01238
1000 Genomes Project 30x 0.01296
The Genome Aggregation Database (gnomAD) 0.01485
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01530
Trans-Omics for Precision Medicine (TOPMed) 0.01558
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BLK | - | - |
GRCh38 GRCh38 GRCh37 |
290 | 464 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000013112.33 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Mar 28, 2016 | RCV000116496.18 | |
Benign (1) |
criteria provided, single submitter
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Mar 3, 2017 | RCV000445395.6 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV001521947.19 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538413.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less)
Method: Genome/Exome Filtration
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 11
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000471329.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Nov 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 11
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV003800468.3
First in ClinVar: Feb 13, 2023 Last updated: Feb 20, 2024 |
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Benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002586218.10
First in ClinVar: Oct 22, 2022 Last updated: May 12, 2024 |
Comment:
BLK: BP4, BS1, BS2
Number of individuals with the variant: 7
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Likely benign
(Jul 23, 2013)
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criteria provided, single submitter
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000150438.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308018.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Mar 03, 2017)
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criteria provided, single submitter
Method: research
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Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
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Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Study: Personalized Diabetes Medicine Program
Accession: SCV000537051.3 First in ClinVar: Mar 14, 2017 Last updated: Dec 11, 2022 |
Comment:
ACMG Criteria:BP4 (6 predictors), PP3 (4 predictors), BS1 (2.5% in African 1.6% in European in 1000g), BS2 (about equal cases and controls in type2diabetesgenetics.org), PS3 … (more)
ACMG Criteria:BP4 (6 predictors), PP3 (4 predictors), BS1 (2.5% in African 1.6% in European in 1000g), BS2 (about equal cases and controls in type2diabetesgenetics.org), PS3 (functional studies show effect) (less)
Number of individuals with the variant: 10
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Likely benign
(Oct 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 11
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002794593.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Sep 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000582792.5
First in ClinVar: Oct 02, 2016 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 22696686, 20981092, 26821283, 23261300, 22995991, 25333069, 19667185, 23224494, 27884173, 31101814, 32028929)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001731387.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 11
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812658.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
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Pathogenic
(Aug 25, 2009)
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no assertion criteria provided
Method: literature only
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MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 11
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000033359.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In affected members of a 5-generation Caucasian family (designated 'F8') segregating autosomal dominant maturity-onset diabetes of the young (MODY11; 613375), Borowiec et al. (2009) identified … (more)
In affected members of a 5-generation Caucasian family (designated 'F8') segregating autosomal dominant maturity-onset diabetes of the young (MODY11; 613375), Borowiec et al. (2009) identified 3 mutations in the BLK gene that occurred together as a haplotype: a G-to-A transition at chr8:11,442,985 in exon 4, resulting in an ala71-to-thr (A71T) substitution; a T-to-G transversion at chr8:11,459,364, at the end of the 3-prime untranslated region (UTR); and a C-to-T transition at chr8:11,468,050, 18 kb from the gene on the 3-prime side. All nucleotide positions are designated according to NCBI36/hg18. The F8 haplotype was also found in 2 (0.003) of 672 Caucasian nondiabetic controls. All 3 mutations decreased in vitro promoter activity in reporter gene experiments; studies in MIN6 beta cells showed that the A71T mutant attenuated the enhancing effect of BLK on insulin content and secretion to the point of being undetectable, and the inducing effect of BLK on the expression of transcription factors PDX1 (600733) and NKX6.1 (602563) was abolished. Noting that the penetrance of the F8 haplotype was 0.33 (2 affected out of 6) among carriers with a body mass index (BMI) less than 28 compared to 0.89 (8 affected out of 9) among carriers with a BMI greater than or equal to 28, Borowiec et al. (2009) suggested that the diabetogenic environment conferred by an increased body weight might be necessary for translation of the beta-cell abnormalities caused by the F8 haplotype into diabetes. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928986.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001800257.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. | Borowiec M | Proceedings of the National Academy of Sciences of the United States of America | 2009 | PMID: 19667185 |
http://www.type2diabetesgenetics.org/variantSearch/launchAVariantSearch/?filters=%5B%7B%22dataset%22%3A%22ExSeq_19k_mdv33%22%2C%22value%22%3A%220%22%2C%22prop%22%3A%22MAC%22%2C%22comparator%22%3A%22%3E%22%2C%22phenotype%22%3A%22T2D%22%7D%2C%7B%22prop%22%3A%22chromosome%22%2C%22value%22%3A%228%3A11405576-11405576%22%2C%22comparator%22%3A%22%3D%22%7D%5D | - | - | - | - |
Text-mined citations for rs55758736 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.