ClinVar Genomic variation as it relates to human health
NM_000975.5(RPL11):c.60_61del (p.Cys21fs)
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_000975.5(RPL11):c.60_61del (p.Cys21fs)
Variation ID: 5752 Accession: VCV000005752.7
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 1p36.11 1: 23692660-23692661 (GRCh38) [ NCBI UCSC ] 1: 24019150-24019151 (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 1, 2024 Aug 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000975.5:c.60_61del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000966.2:p.Cys21fs frameshift NM_001199802.1:c.57_58del NP_001186731.1:p.Cys20fs frameshift NC_000001.11:g.23692660CT[1] NC_000001.10:g.24019150CT[1] NG_011741.2:g.5882CT[1] LRG_1140:g.5882CT[1] LRG_1140t1:c.60_61del LRG_1140p1:p.Cys21fs - Protein change
- C20fs, C21fs
- Other names
- NM_000975.5:c.60_61del
- Canonical SPDI
- NC_000001.11:23692659:CTCT:CT
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Comment on variant
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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RPL11 | - | - |
GRCh38 GRCh37 |
155 | 188 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (2) |
criteria provided, single submitter
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May 4, 2022 | RCV000006108.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 10, 2023 | RCV002354149.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 14, 2023 | RCV003415663.4 |
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
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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
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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
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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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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: curation
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Diamond-Blackfan anemia 7
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV002507058.1
First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
Comment:
The heterozygous p.Cys21SerfsTer33 variant in RPL11 was identified by our study in one individual with Diamond-Blackfan anemia 7 (DBA7). Trio exome analysis showed this variant … (more)
The heterozygous p.Cys21SerfsTer33 variant in RPL11 was identified by our study in one individual with Diamond-Blackfan anemia 7 (DBA7). Trio exome analysis showed this variant to be de novo. The variant has been reported in 5 individuals of Italian and unknown ethnicity with DBA7 (PMID: 19773262, 19061985), but was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 21 and leads to a premature termination codon 33 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the RPL11 gene is a moderately established disease mechanism in DBA7. In summary, this variant meets criteria to be classified as pathogenic for DBA7 in an autosomal dominant manner based on the predicted loss of function impact of the variant and its de novo occurrence. ACMG/AMP Criteria applied: PS2, PVS1_strong, PM2, PS4_supporting (Richards 2015). (less)
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Pathogenic
(Jul 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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RPL11-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004106986.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The RPL11 c.60_61delCT variant is predicted to result in a frameshift and premature protein termination (p.Cys21Serfs*33). This variant has been reported in individuals with Diamond-Blackfan … (more)
The RPL11 c.60_61delCT variant is predicted to result in a frameshift and premature protein termination (p.Cys21Serfs*33). This variant has been reported in individuals with Diamond-Blackfan anaemia (Gazda et al. 2008. PubMed ID: 19061985; Muramatsu et al. 2017. PubMed ID: 28102861; Gálvez et al. 2021. PubMed ID: 33718801). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in RPL11 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Aug 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Diamond-Blackfan anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004291755.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys21Serfs*33) in the RPL11 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Cys21Serfs*33) in the RPL11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPL11 are known to be pathogenic (PMID: 19061985, 19773262). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Diamond-Blackfan anemia (PMID: 19061985, 28102861). This variant is also known as c.58_59delCT. ClinVar contains an entry for this variant (Variation ID: 5752). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 25, 2014)
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criteria provided, single submitter
Method: clinical testing
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Diamond-Blackfan anemia
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002656170.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.60_61delCT pathogenic mutation, located in coding exon 2 of the RPL11 gene, results from a deletion of two nucleotides between nucleotide positions 60 and … (more)
The c.60_61delCT pathogenic mutation, located in coding exon 2 of the RPL11 gene, results from a deletion of two nucleotides between nucleotide positions 60 and 61, causing a translational frameshift with a predicted alternate stop codon (p.C21Sfs*33). This pathogenic mutation was first described in an individual with Diamond-Blackfan anemia with a ventricular septal defect (VSD) and a narrow pulmonary artery who was responsive to steroid therapy; the proband's mother and maternal grandmother also carried the mutation and had triphalangeal thumbs (Gazda HT et al. Am J Hum Genet. 2008;83(6):769-80). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). (less)
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Pathogenic
(Dec 01, 2008)
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no assertion criteria provided
Method: literature only
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DIAMOND-BLACKFAN ANEMIA 7
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026290.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 02, 2021 |
Comment on evidence:
In a female patient in whom Diamond-Blackfan anemia (DBA7; 612562) was diagnosed at 9 months of age, who also had triphalangeal thumbs, ventricular septal defect, … (more)
In a female patient in whom Diamond-Blackfan anemia (DBA7; 612562) was diagnosed at 9 months of age, who also had triphalangeal thumbs, ventricular septal defect, and a narrow pulmonary artery, Gazda et al. (2008) identified heterozygosity for a 2-bp deletion (60delCT) in exon 2 of the RPL11 gene, resulting in a frameshift causing a termination sequence at codon 53. The mutation was also identified in her affected mother and grandmother, who both had associated triphalangeal thumbs, but was not found in at least 150 controls. (less)
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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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Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. | Muramatsu H | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28102861 |
Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | Quarello P | Haematologica | 2010 | PMID: 19773262 |
Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. | Gazda HT | American journal of human genetics | 2008 | PMID: 19061985 |
Text-mined citations for rs1570566590 ...
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.
ClinGen staff contributed the HGVS expression for this variant.