ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3100_3101del (p.Asp1033_Ile1034insTer) (rs1555283051)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574885 SCV000666113 pathogenic Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing The c.3100_3101delAT variant, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 3100 to 3101, causing a translational frameshift with a predicted alternate stop codon. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000698664 SCV000827344 pathogenic Hereditary breast and ovarian cancer syndrome 2020-02-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile1034*) 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 not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 481578). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000698664 SCV001372329 likely pathogenic Hereditary breast and ovarian cancer syndrome 2020-06-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3100_3101delAT (p.Ile1034X) 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. The variant allele was found at a frequency of 1.2e-05 in 249650 control chromosomes. To our knowledge, no occurrence of c.3100_3101delAT in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two 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 likely pathogenic.

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