ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1644G>A (p.Gln548=) (rs55986646)

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Total submissions: 7
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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) RCV000112947 SCV000578019 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0032 (East Asian), derived from ExAC (2014-12-17).
Invitae RCV000588688 SCV000071864 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162904 SCV000213391 likely benign Hereditary cancer-predisposing syndrome 2014-12-10 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501303 SCV000591758 benign not specified 2015-06-10 criteria provided, single submitter clinical testing
Color RCV000162904 SCV000683434 benign Hereditary cancer-predisposing syndrome 2015-11-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588688 SCV000694551 likely benign not provided 2017-08-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1644G>A (p.Gln548Gln) variant (also known as 1872G>A) involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict a significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC and in the literature in 29/121652 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.003239 (28/8644). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In literature, this variant has been reported in multiple HBOC patients without strong evidence for or against pathogenicity (Suter_BRCA1&2_Cancer Epidemiology, Biomarkers & Prevention_2004, Thirthagiri_BRCA1&2_Breast Cancer Res_2008). This variant is reported to co-occur with BRCA2 c.1212delT/p.Asn404LysfsX26 variant (pathogenic in ClinVar, not in our internal database) in the UMD-BRCA2 database in three individuals, strongly suggesting a benign outcome. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. Taken together, this variant is currently classified as likely benign.
Breast Cancer Information Core (BIC) (BRCA2) RCV000112947 SCV000145904 benign Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing

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