ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.430_432GTT[1] (p.Val145del) (rs80359442)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417373 SCV000210543 likely benign not specified 2017-02-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000164811 SCV000215493 likely benign Hereditary cancer-predisposing syndrome 2017-11-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000202422 SCV000257480 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-02 criteria provided, single submitter clinical testing
Color RCV000164811 SCV000688869 benign Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000417373 SCV000918856 uncertain significance not specified 2017-09-22 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.433_435delGTT (p.Val145del) variant causes an in-frame deletion of one amino acid residue in exon 5 of the BRCA2 protein. This variant was found in 5/276612 control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.004% (5/126408), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.07503%). The variant of interest has been observed in affected individuals via publications (Alsop_2012, Borg_2010), although limited information is provided (lack of co-occurrence and/or cosegregation data were included), thus limiting independent evaluation of causality. Carney_2010 does report the variant in an unaffected daughter (mother carried variant and diagnosed with BrC), the daughter is younger than the average age of onset, 26 y/o vs. 50 y/o. Reputable databases have reported the variant to co-occur with two different potentially pathogenic BRCA1 variants, c.-81_-1dup and c.5207T>C (scored DV). The variant of interest was functionally assessed and found not to affect splicing (Houdayer_2012). In addition, multiple clinical diagnostic laboratories/reputable databases have cited the variant with conflicting classifications, "uncertain significance," or "likely benign." Therefore, this variant has been classified as a "Variant of Uncertain Significance - Possibly Benign."
Sharing Clinical Reports Project (SCRP) RCV000031476 SCV000054081 likely benign Breast-ovarian cancer, familial 2 2012-06-11 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031476 SCV000146839 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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