ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3900_3902del (p.Met1300_Thr1301delinsIle) (rs397507697)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044300 SCV000072313 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-03-31 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 11 of the BRCA2 mRNA (c.3900_3902del). This leads to the deletion of 2 amino acid residue (methionine and threonine) and insertion of one amino acid residue (isoleucine) in the BRCA2 protein (p.Met1300_Thr1301delinsIle) but otherwise preserves the integrity of the reading frame. This variant has been reported in the literature and is present in population databases (rs397507697, 0.003%). This variant was reported in an individual affected with breast cancer (PMID: 22762150) and in affected patients in the Universal Mutation Database (PMID: 22144684). However, one pathogenic allele was identified in the BRCA1 gene, which suggests that this c.3900_3902del change in BRCA2 was not the primary cause of disease in this individual. In summary, this is a rare missense change with uncertain impact on protein function. Although the observation of co-occurrence with a pathogenic mutation is suggestive of non-pathogenicity, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000218170 SCV000276702 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Insufficient evidence
Color RCV000218170 SCV000683591 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
Counsyl RCV000662911 SCV000785840 uncertain significance Breast-ovarian cancer, familial 2 2017-12-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758891 SCV000887805 uncertain significance not provided 2018-08-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780034 SCV000917047 uncertain significance not specified 2018-11-01 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3900_3902delGAC (p.Met1300_Thr1301delinsIle) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2.6e-05 in 228420 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3900_3902delGAC has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Demange_2001, Lecarpentier_2012). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.5030_5033delCTAA, p.Thr1677IlefsX2 via UMD), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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