Submissions for variant NM_000059.4(BRCA2):c.4412_4414del (p.Arg1471del)

dbSNP: rs886039317

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255607	SCV000321459	uncertain significance	not provided	2019-05-24	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29335924, 18844490, 31159747)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000469480	SCV000549655	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-12-07	criteria provided, single submitter	clinical testing	This variant, c.4412_4414del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Arg1471del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29335924, 31159747). ClinVar contains an entry for this variant (Variation ID: 265056). 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.
Ambry Genetics	RCV000567428	SCV000666003	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-02	criteria provided, single submitter	clinical testing	The c.4412_4414delGAA variant (also known as p.R1471del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame GAA deletion at nucleotide positions 4412 to 4414. This results in the in-frame deletion of an arginine at codon 1471. In one study, this alteration was detected in a healthy (no breast or ovarian cancer diagnosis) Croatian female aged between 64 and 100 years (Cvok ML, et al. Clin. Chem. Lab. Med. 2008;46(10):1376-83). This alteration has also been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is poorly 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). Based on the available evidence, the clinical significance of this variant remains unclear.
GeneKor MSA	RCV000567428	SCV000821939	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000567428	SCV000909498	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-16	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid at codon 1471 of the BRCA2 protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with BRCA2-associated cancers (PMID: 29335924; Color internal data) and in an unaffected healthy control (PMID 18844490). 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.
Baylor Genetics	RCV003475857	SCV004211934	uncertain significance	Familial cancer of breast	2023-09-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995740	SCV004845678	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-05-04	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid of the BRCA2 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with advanced cancer including breast cancer (PMID 28873162, 29335924) and in unaffected healthy control (PMID 18844490). 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.