ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3273_3276del (p.Leu1091fs)

dbSNP: rs80359382
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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) RCV000113157 SCV000300610 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000484736 SCV000570329 pathogenic not provided 2016-05-12 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in BRCA2 is denoted c.3273_3276delATTT at the cDNA level and p.Leu1091PhefsX12 (L1091FfsX12) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3501del4. The normal sequence, with the bases that are deleted in braces, is TGTT[ATTT]TCCA. The deletion causes a frameshift which changes a Leucine to a Phenylalanine at codon 1091 and creates a premature stop codon at position 12 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589349 SCV000694686 likely pathogenic Hereditary breast ovarian cancer syndrome 2016-01-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002444501 SCV002612556 pathogenic Hereditary cancer-predisposing syndrome 2022-07-11 criteria provided, single submitter clinical testing The c.3273_3276delATTT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 3273 to 3276, causing a translational frameshift with a predicted alternate stop codon (p.L1091Ffs*12). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Baylor Genetics RCV003473329 SCV004212836 likely pathogenic Familial cancer of breast 2022-02-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000589349 SCV004517550 pathogenic Hereditary breast ovarian cancer syndrome 2023-06-20 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 51442). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1091Phefs*12) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).
Breast Cancer Information Core (BIC) (BRCA2) RCV000113157 SCV000146206 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing

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