ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6350_6351GT[1] (p.Val2118fs) (rs80359576)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217850 SCV000273098 pathogenic Hereditary cancer-predisposing syndrome 2014-12-01 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113578 SCV000146833 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000217850 SCV000906925 pathogenic Hereditary cancer-predisposing syndrome 2018-04-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113578 SCV000327400 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113578 SCV000301021 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000237021 SCV000293335 pathogenic not provided 2015-10-27 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.6352_6353delGT at the cDNA level and p.Val2118LysfsX10(V2118KfsX10) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTGT[GT]AAAC. The deletion causes a frameshift, which changes a Valine to a Lysine at codon 2118, and creates a premature stop codon at position 10 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.6352_6353delGT, also reported as BRCA2 6580delGT using alternate nomenclature, has been reported in individuals with familial breast and/or ovarian cancer (Piek 2003, Tea 2014). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044921 SCV000918807 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-18 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6352_6353delGT (p.Val2118LysfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.6405_6409delCTTAA (p.Asn2135fsX3), c.6449_6450delAA (p.Lys2150fsX25), c.6468_6469delTC (p.Gln2157fsX18)). The variant was absent in 241066 control chromosomes (in gnomAD). The c.6352_6353delGT has been reported in the literature in individuals with individual/family history of Breast and Ovarian Cancer (Piek 2003, Hermsen 2006, Tea 2014). These data indicate that the variant is very likely to be associated with disease. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000044921 SCV000072934 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val2118Lysfs*10) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with breast or ovarian cancer (PMID: 14574155, 24156927). This variant is also known as 6580delGT in the literature. ClinVar contains an entry for this variant (Variation ID: 52071). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000237021 SCV000600696 pathogenic not provided 2017-03-09 criteria provided, single submitter clinical testing

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