ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7559G>A (p.Arg2520Gln) (rs80358982)

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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 RCV000130121 SCV000184953 likely benign Hereditary cancer-predisposing syndrome 2018-04-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000082974 SCV000147122 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000130121 SCV000689054 likely benign Hereditary cancer-predisposing syndrome 2017-10-27 criteria provided, single submitter clinical testing
Counsyl RCV000082974 SCV000489088 uncertain significance Breast-ovarian cancer, familial 2 2016-08-17 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160244 SCV000592124 uncertain significance not specified 2014-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000160244 SCV000210656 likely benign not specified 2017-06-14 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.
Integrated Genetics/Laboratory Corporation of America RCV000585960 SCV000695079 likely benign not provided 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7559G>A (p.Arg2520Gln) variant involves the alteration of a conserved nucleotide and results in a replacement of an Arg with a Gln located in the helical domain of BRCA2. 4/5 in-silico tools predict this variant to be damaging. 5/5 programs in Alamut predict the variant not to affect normal splicing. These splicing predictions have been confirmed by analyzing the RNA from patients carrying this variant (Houdayer_2012). The variant was found in 2/120722 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). UMD reports one patient who carries this variant and BRCA2 c.8485C>T/p.Gln2829X (pathogenic in ClinVar), which suggests the variant to be in the benign spectrum. A functional study showed that the variant increases homology-directed recombination repair (HDR) activity when expressed in BRCA2 deficient cells comparable to wild type (Farrugia_2008) further supporting neutrality. Multiple clinical laboratories/reputable databases provide conflicting classifications, ranging from VUS to benign. Taken all lines of evidence together, the variant was classified as likely benign.
Invitae RCV000196768 SCV000253038 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-29 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082974 SCV000115048 benign Breast-ovarian cancer, familial 2 2014-02-20 no assertion criteria provided clinical testing

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