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GRCh37/hg19 5q35.2-35.3(chr5:176516440-177773252)x3 AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 8, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002474595.1

Allele description [Variation Report for GRCh37/hg19 5q35.2-35.3(chr5:176516440-177773252)x3]

GRCh37/hg19 5q35.2-35.3(chr5:176516440-177773252)x3

Genes:
Variant type:
copy number gain
Cytogenetic location:
5q35.2-35.3
Genomic location:
Chr5: 176516440 - 177773252 (on Assembly GRCh37)
Preferred name:
GRCh37/hg19 5q35.2-35.3(chr5:176516440-177773252)x3
HGVS:

    Condition(s)

    Synonyms:
    none provided
    Identifiers:
    MedGen: CN517202

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV002771991Quest Diagnostics Nichols Institute San Juan Capistrano
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)
    Likely pathogenic
    (Jun 8, 2021)
    unknownclinical testing

    PubMed (1)
    [See all records that cite this PMID]

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

    Citations

    PubMed

    Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

    Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, Raca G, Ritter DI, South ST, Thorland EC, Pineda-Alvarez D, Aradhya S, Martin CL.

    Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6. Erratum in: Genet Med. 2021 Nov;23(11):2230.

    PubMed [citation]
    PMID:
    31690835
    PMCID:
    PMC7313390

    Details of each submission

    From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002771991.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (1)

    Description

    The copy number gain of 5q35.2q35.3 involves multiple protein-coding genes, including NSD1 (OMIM 606681), SLC34A1 (OMIM 182309), and F12 (OMIM 610619). Haploinsufficiency of NSD1 is associated with Sotos syndrome 1 (OMIM 117550). The NSD1 gene however is not currently classified as triplosensitive although it is contained within the shortest region of overlap within a larger 5q35 recurrent region associated with \reversed\" Sotos syndrome phenotype, commonly including short stature, microcephaly, delayed bone age, and developmental delay/intellectual disability. Case reports with smaller overlapping duplications of this region, and include NSD1, were described with Silver-Russell syndrome (SRS) and three with reverse Sotos syndrome (Kirchhoff et al., Eur J Med Genet. Jan-Feb2007;50(1):33-42. PMID: 17090394; Reis et al., Genet Mol Res. 2017Jan 23;16(1). PMID: 28128410; Sachwitz et al., Clin Genet. 2017Jan;91(1):73-78. PMID: 27172843; Rosenfeld et al., Mol Syndromol.2013 Jan;3(6):247-54. PMID: 23599694). The individual with SRS carried a de novo 381 Kb duplication. Two individuals with reverse Sotos syndrome carried de novo duplications and one carried a maternally inherited duplication. All patients had phenotypes involving growth retardation and facial anomalies. Heterozygous sequence variants of SLC34A1 and F12 are associated with autosomal dominant disorders, hypophosphatemic nephrolithiasis/osteoporosis-1 (OMIM 612286) and hereditary angioedema type III (OMIM 610618), respectively. There are no similar copy number gains of this region in the general populations of the Database of Genomic Variants. Thus, the clinical significance of this copy number variant (CNV) is likely pathogenic."

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

    Last Updated: Mar 26, 2023