Description
The BARD1 p.Asn118Ser variant was not identified in the literature nor was it identified in the Cosmic, MutDB, databases. The variant was identified in dbSNP (ID: rs142864491) as “With Uncertain significance allele,” ClinVar (classified as uncertain significance by GeneDx, Ambry Genetics, Invitae), Zhejiang Colon Cancer Database. The variant was identified in control databases in 13 of 276666 chromosomes at a frequency of 0.000047 in the following populations: European (Non-Finnish) in 12 of 126474 chromosomes (freq. 0.00009), and African in 1 of 24008 chromosomes (freq. 0.00004) (Genome Aggregation Consortium Feb 27, 2017). The p.Asn118 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
| # | 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 | | 1 | not provided | not provided | not provided |
