Description
The BARD1 p.Arg659= variant was identified in 50 of 25,074 proband chromosomes (frequency: 0.002) from individuals or families with basal cell carcinoma and hereditary breast and ovarian cancer and was present in 14 of 9414 control chromosomes (frequency: 0.001) from healthy individuals (Suszynska 2019, Cho 2018). The variant was identified in dbSNP (rs147215925) as “with other allele” and ClinVar (classified as likely benign by GeneDx, Ambry Genetics, Mendelics and 4 other submitters, benign by Invitae, Color and Quest Diagnostics and uncertain significance by Integrated Genetics and Prevention Genetics). The variant was identified in control databases in 576 of 282,800 chromosomes (1 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 81 of 10,366 chromosomes (freq: 0.008), Other in 24 of 7216 chromosomes (freq: 0.003), European in 398 of 129,128 chromosomes (freq: 0.003), Finnish in 33 of 25,118 chromosomes (freq: 0.001), Latino in 30 of 35,438 chromosomes (freq: 0.0008), African in 9 of 24,968 chromosomes (freq: 0.0004), South Asian in 1 of 30,612 chromosomes (freq: 0.00003), while the variant was not observed in the East Asian population. The p.Arg659= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
