Submissions for variant NM_000059.4(BRCA2):c.9113_9115dup (p.Leu3038dup)

dbSNP: rs80359749

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131277	SCV000186245	uncertain significance	Hereditary cancer-predisposing syndrome	2024-12-05	criteria provided, single submitter	clinical testing	The c.9113_9115dupTAC variant (also known as p.L3038dup), located in coding exon 22 of the BRCA2 gene, results from an in-frame duplication of TAC at nucleotide positions 9113 to 9115. This results in the duplication of an extra residue between codons 3038 and 3039. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228966	SCV000283356	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-26	criteria provided, single submitter	clinical testing
Counsyl	RCV000114049	SCV000488191	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2016-02-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000759683	SCV000567948	uncertain significance	not provided	2021-07-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12228710, 27535533)
Color Diagnostics, LLC DBA Color Health	RCV000131277	SCV000689176	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-12	criteria provided, single submitter	clinical testing	This variant causes an in-frame duplication of amino acid leucine 3038 in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/280326 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759683	SCV000889171	uncertain significance	not provided	2023-01-10	criteria provided, single submitter	clinical testing	The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00011 (4/35258 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000486391	SCV001338628	uncertain significance	not specified	2024-08-05	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.9113_9115dupTAC (p.Leu3038dup) results in an in-frame duplication that is predicted to duplicate one amino acids into the encoded protein. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 248918 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9113_9115dupTAC has been reported in the literature in an individual affected with Breast Cancer (Perez-Ibave_2023). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 36833268). ClinVar contains an entry for this variant (Variation ID: 126201). Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002483176	SCV002786816	uncertain significance	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2021-10-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759683	SCV004564863	likely benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000114049	SCV004846125	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-11-02	criteria provided, single submitter	clinical testing	This variant causes an in-frame duplication of amino acid leucine 3038 in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/280326 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV004566990	SCV005059202	uncertain significance	Familial cancer of breast	2023-11-03	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114049	SCV000147541	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing