Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000044498 | SCV000072511 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000074530 | SCV000108615 | likely benign | not specified | 2018-02-21 | 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 | RCV000130783 | SCV000185676 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign) |
Department of Pathology and Laboratory Medicine, |
RCV000074530 | SCV000591929 | uncertain significance | not specified | 2014-01-22 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000074530 | SCV000694805 | benign | not specified | 2020-11-23 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.4828G>A (p.Val1610Met) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 250074 control chromosomes, predominantly at a frequency of 0.00021 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (9.6e-05 vs 0.00075), allowing no conclusion about variant significance. c.4828G>A has been reported in the literature in individuals affected with Breast and Ovarian Cancer (example, Lee_2008, Kote-Jarai_2011, Simard_2007, Caminsky_2016, Jarhelle_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least two known co-occurrences with other pathogenic variant(s) have been reported (UMD database-BRCA1 c.4327C>T, p.Arg1443*; BIC database-BRCA1 c.3481_3491delGAAGATACTAG, p.Glu1161_Ser1164?fs), providing supporting evidence for a benign role. Two recent reports from the CAGI5 (fifth Critical Assessment of Genome Interpretation) challenge have classified this variant as likely benign in a prediction protocol that includes assessment of the impact of this variant on splicing and protein function using four sets of predictors (Padilla_2019, Cline_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Four have classified the variant as Benign/Likely Benign and two classified the variant as uncertain significance citing overlapping references utilized in the context of this evaluation. Based on the evidence outlined above, the variant was re-classified as benign. |
Color Health, |
RCV000130783 | SCV000910745 | benign | Hereditary cancer-predisposing syndrome | 2017-01-25 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV001112023 | SCV001269637 | uncertain significance | Fanconi anemia, complementation group D1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Clinical Services Laboratory, |
RCV000031508 | SCV001269638 | uncertain significance | Breast-ovarian cancer, familial 2 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Sharing Clinical Reports Project |
RCV000031508 | SCV000054113 | benign | Breast-ovarian cancer, familial 2 | 2009-08-31 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031508 | SCV000146488 | uncertain significance | Breast-ovarian cancer, familial 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
Department of Medical Genetics, |
RCV000031508 | SCV000301448 | uncertain significance | Breast-ovarian cancer, familial 2 | 2016-05-01 | no assertion criteria provided | clinical testing |