ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1389_1390del (p.Val464fs) (rs80359283)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214525 SCV000273209 pathogenic Hereditary cancer-predisposing syndrome 2017-05-05 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077255 SCV000145863 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000214525 SCV000683420 pathogenic Hereditary cancer-predisposing syndrome 2015-06-10 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077255 SCV000326547 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077255 SCV000282356 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000160277 SCV000210730 pathogenic not provided 2018-06-14 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.1389_1390delAG at the cDNA level and p.Val464GlyfsX3 (V464GfsX3) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAC[delAG]TGGT. The deletion causes a frameshift, which changes a Valine to a Glycine at codon 464, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.1389_1390delAG, also published as BRCA2 1617_1618delAG or BRCA2 1617delAG using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian cancer (Goelen 1999, Claes 2004, Machackova 2008). We consider this variant to be pathogenic.
GeneKor MSA RCV000585683 SCV000693557 pathogenic Familial cancer of breast 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000043794 SCV000916856 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1389_1390delAG (p.Val464GlyfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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 (eg. c.1842dupT/p.Asn615X). The variant was absent in 243428 control chromosomes. c.1389_1390delAG has been reported in the literature in multiple individuals affected with Hereditary Breast and/or Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000043794 SCV000071807 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val464Glyfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in families affected with breast and ovarian cancer (PMID: 10227398, 24549055, 16683254, 15024741, 26681312). It is also known as 1617delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 51113). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077255 SCV000296651 pathogenic Breast-ovarian cancer, familial 2 2015-11-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160277 SCV000888977 pathogenic not provided 2015-11-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077255 SCV000109052 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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