Submissions for variant NM_000059.4(BRCA2):c.5229_5231del (p.Ser1744del)

dbSNP: rs397507349

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129999	SCV000184823	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-12	criteria provided, single submitter	clinical testing	The c.5229_5231delTAG variant (also known as p.S1744del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame TAG deletion at nucleotide positions 5229 to 5231. This results in the in-frame deletion of a serine at codon 1744. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588412	SCV000694846	uncertain significance	not provided	2016-12-27	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.5229_5231delTAG (p.Ser1744del) variant involves the deletion of three adjacent nucleotides resulted in frame deletion of one amino acid. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp40. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 120118 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance, and SCRP classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Diagnostics, LLC DBA Color Health	RCV000129999	SCV000903716	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-23	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid, serine 1744, in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.1021 and 1.4673, respectively (PMID: 31131967). This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000806665	SCV000946678	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-12-17	criteria provided, single submitter	clinical testing	This variant, c.5229_5231del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Ser1744del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 37953). 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.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000806665	SCV002026115	uncertain significance	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477035	SCV002776545	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	2022-04-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000031534	SCV004845788	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, serine 1744, in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.1021 and 1.4673, respectively (PMID: 31131967). This variant has not been identified 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.
Sharing Clinical Reports Project (SCRP)	RCV000031534	SCV000054139	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2008-08-26	no assertion criteria provided	clinical testing