ClinVar

Description

The POLD1 p.Val555= variant was not identified in the literature. The variant was identified in dbSNP (rs150238541) as “with likely benign allele” and ClinVar (classified as likely benign by Ambry Genetics, GeneDx, True Health Diagnostics and 2 other submitters; and as benign by Invitae and Prevention Genetics). The variant was identified in control databases in 206 of 279,020 chromosomes (2 homozygous) at a frequency of 0.0007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 43 of 30,490 chromosomes (freq: 0.001), European in 142 of 126,522 chromosomes (freq: 0.001), Other in 4 of 7138 chromosomes (freq: 0.0006), Finnish in 13 of 24,740 chromosomes (freq: 0.0005), Ashkenazi Jewish in 1 of 10,192 chromosomes (freq: 0.0001), African in 2 of 24,900 chromosomes (freq: 0.00008), and Latino in 1 of 35,130 chromosomes (freq: 0.00003), while it was not observed in the East Asian population. The p.Val555= 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.