ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7025_7026del (p.Gln2342fs) (rs80359634)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574666 SCV000661162 pathogenic Hereditary cancer-predisposing syndrome 2017-12-04 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) RCV000077397 SCV000147004 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000574666 SCV000911870 pathogenic Hereditary cancer-predisposing syndrome 2017-11-22 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077397 SCV000327581 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) RCV000077397 SCV000301122 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000485273 SCV000568480 pathogenic not provided 2017-11-09 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.7025_7026delAA at the cDNA level and p.Gln2342ArgfsX17 (Q2342RfsX17) at the protein level. The normal sequence, with the bases that are deleted in braces, is CGTC[AA]GAGA. The deletion causes a frameshift, which changes a Glutamine to an Arginine at codon 2342, and creates a premature stop codon at position 17 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.7025_7026delAA, also reported as 7253delAA using alternate nomenclature, has been reported in individuals with early-onset, familial, male, and bilateral breast cancer (Friedman 1997, Schoumacher 2001, Borg 2010). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045123 SCV000695029 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-28 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7025_7026delAA (p.Gln2342Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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 (e.g. c.7110dupA/ p.Ser2371fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120826 control chromosomes. However, it has been reported in many affected individuals and multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000045123 SCV000073136 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 14 of the BRCA2 mRNA (c.7025_7026delAA), causing a frameshift at codon 2342. This creates a premature translational stop signal (p.Gln2342Argfs*17) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with breast cancer (PMID: 9012404, 20104584). This variant is referred to as 7253 2bp deletion in the literature. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000485273 SCV000296736 pathogenic not provided 2015-02-09 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077397 SCV000109194 pathogenic Breast-ovarian cancer, familial 2 2007-10-31 no assertion criteria provided clinical testing

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