Submissions for variant NM_000465.4(BARD1):c.1314+5G>T

dbSNP: rs868089048

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000758764	SCV000567651	uncertain significance	not provided	2016-05-24	criteria provided, single submitter	clinical testing	This variant is denoted BARD1 c.1314+5G>T or IVS4+5G>T and consists of a G>T nucleotide substitution at the +5 position of intron 4 of the BARD1 gene. Multiple in silico models predict this variant to weaken the nearby natural splicing donor site, and to possibly cause abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as either a mutation or a benign polymorphism. The guanine (G) nucleotide that is altered is conserved across species. Based on the currently available information, we consider BARD1 c.1314+5G>T to be a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687118	SCV000814670	uncertain significance	Familial cancer of breast	2025-01-29	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the BARD1 gene. It does not directly change the encoded amino acid sequence of the BARD1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 419682). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with inconclusive levels of altered splicing (internal data). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758764	SCV000887583	uncertain significance	not provided	2018-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001010920	SCV001171185	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-07	criteria provided, single submitter	clinical testing	The c.1314+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 4 in the BARD1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV001010920	SCV001341177	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-21	criteria provided, single submitter	clinical testing	This variant causes a G to T nucleotide substitution at the +5 position of intron 4 of the BARD1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. However, this prediction has not been confirmed in published RNA studies. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000758764	SCV002009157	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing