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GRCh38/hg38 2q21.3(chr2:135162318-135164794)x1 AND Warburg micro syndrome 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 24, 2023
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:
RCV003327706.2

Allele description [Variation Report for GRCh38/hg38 2q21.3(chr2:135162318-135164794)x1]

GRCh38/hg38 2q21.3(chr2:135162318-135164794)x1

Gene:
RAB3GAP1:RAB3 GTPase activating protein catalytic subunit 1 [Gene - OMIM - HGNC]
Variant type:
copy number loss
Cytogenetic location:
2q21.3
Genomic location:
Chr2: 135162318 - 135164794 (on Assembly GRCh38)
Preferred name:
GRCh38/hg38 2q21.3(chr2:135162318-135164794)x1
HGVS:

    Condition(s)

    Name:
    Warburg micro syndrome 1 (WARBM1)
    Synonyms:
    Microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy and hypogenitalism
    Identifiers:
    MONDO: MONDO:0010822; MedGen: C1838625; Orphanet: 2510; OMIM: 600118

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    Assertion and evidence details

    Help
    Submission AccessionSubmitterReview Status
    (Assertion method)    		Clinical Significance
    (Last evaluated)    		OriginMethodCitations
    SCV004034236Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)    		Uncertain significance
    (Aug 24, 2023)     		unknownresearch

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

    Help

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedunknownyesnot providednot providednot providednot providednot providedresearch

    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. doi: 10.1038/s41436-021-01150-9.

    PubMed [citation]
    PMID:
    31690835
    PMCID:
    PMC7313390

    Details of each submission

    From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV004034236.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedresearch PubMed (1)

    Description

    A heterozygous deletion of exons 20-23 in RAB3GAP1 (NM_012233.3) was identified by exome sequencing in one individual with Warburg micro syndrome, confirmed in trans with a likely pathogenic variant (p.Leu798ArgfsTer7) ([GRCh 38] chr2:135162318_135164794x1). The presence of this deletion was validated by ddPCR. These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This intragenic deletion of 4 exons is not predicted to alter the protein reading-frame and it is unclear if this deletion will impact the protein. Loss of function of RAB3GAP1 is an established disease mechanism in autosomal recessive Warburg micro syndrome (https://search.clinicalgenome.org/kb/gene-dosage). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.45 points, 3: 0 points, 4-5: 0.30 points; Total: 0.75 points; Riggs 2020 (PMID: 31690835).

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

    Last Updated: Mar 30, 2024