Submissions for variant NM_000465.4(BARD1):c.559CCT[1] (p.Pro188del)

dbSNP: rs1553622614

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523156	SCV000618488	uncertain significance	not provided	2017-05-19	criteria provided, single submitter	clinical testing	This in-frame deletion of three nucleotides in BARD1 is denoted c.562_564delCCT at the cDNA level and p.Pro188del (P188del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCCT[delCCT]GCAG. This deletion occurs in a region that is not conserved and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. 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 BARD1 Pro188del to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853629	SCV002274759	uncertain significance	Familial cancer of breast	2021-08-23	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.562_564del, results in the deletion of 1 amino acid(s) of the BARD1 protein (p.Pro188del), but otherwise preserves the integrity of the reading frame.
Baylor Genetics	RCV001853629	SCV005054584	uncertain significance	Familial cancer of breast	2024-02-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004609420	SCV005098896	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-08	criteria provided, single submitter	clinical testing	The c.562_564delCCT variant (also known as p.P188del) is located in coding exon 4 of the BARD1 gene. This variant results from an in-frame CCT deletion at nucleotide positions 562 to 564. This results in the in-frame deletion of a proline at codon 188. 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). Based on the available evidence, the clinical significance of this variant remains unclear.