Submissions for variant NM_000059.4(BRCA2):c.6711TGA[1] (p.Asp2238del)

dbSNP: rs786202738

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165702	SCV000216443	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-27	criteria provided, single submitter	clinical testing	The c.6714_6716delTGA variant (also known as p.D2238del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame TGA deletion at nucleotide positions 6714 to 6716. This results in the in-frame deletion of an aspartic acid at codon 2238. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (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.
GeneDx	RCV000218848	SCV000279516	uncertain significance	not specified	2017-03-21	criteria provided, single submitter	clinical testing	This in-frame deletion of three nucleotides in BRCA2 is denoted c.6714_6716delTGA at the cDNA level and p.Asp2238del (D2238del) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 6942_6944delTGA. The normal sequence, with the bases that are deleted in braces, is ATGA[TGA]ACTG. This deletion of a single Aspartic Acid residue occurs at a position that is not conserved and is not located in a known functional domain (UniProt). This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or a benign polymorphism. However, it was observed in the post-chemotherapy breast tumor of an individual with triple negative breast cancer (Balko 2014). Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRCA2 Asp2238del to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464960	SCV000549572	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-09-30	criteria provided, single submitter	clinical testing	Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 186159). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs786202738, gnomAD 0.007%). This variant, c.6714_6716del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Asp2238del), but otherwise preserves the integrity of the reading frame.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985572	SCV001133874	uncertain significance	not provided	2018-11-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165702	SCV001355521	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-24	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid from 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 1/251318 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000218848	SCV001554631	uncertain significance	not specified	2021-03-22	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.6714_6716delTGA (p.Asp2238del) 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 4e-06 in 251318 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6714_6716delTGA in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five 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.
Baylor Genetics	RCV003474868	SCV004211802	uncertain significance	Familial cancer of breast	2024-03-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000238873	SCV004844301	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-09-04	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid from 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 1/251318 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000218848	SCV005090051	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000238873	SCV000297547	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-09-28	no assertion criteria provided	clinical testing