ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4936_4937del (p.Glu1646fs) (rs431825323)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000082932 SCV000300802 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000165590 SCV000216324 pathogenic Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Integrated Genetics/Laboratory Corporation of America RCV000589045 SCV000694812 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-20 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4936_4937delGA (p.Glu1646Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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.4965C>G, p.Tyr1655X; c.5042_5043delTG, p.Val1681fs). One in silico tool predicts a damaging outcome for this variant. The variant of interest has not been found in a large, broad control population, ExAC in 119240 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Variant at the same location c.4936_4939delGAAA/p.Glu1646fsX23 has been reported in multiple affected individuals and has been classified as pathogenic by multiple clinical diagnostic laboratories/reputable databases, suggesting the location these variants reside is a mutation hotspot. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758901 SCV000887830 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082932 SCV000115006 pathogenic Breast-ovarian cancer, familial 2 2012-10-09 no assertion criteria provided clinical testing

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