Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV000503751 | SCV000592767 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ala1302Ala variant was not identified in the literature nor was it identified in the - Clinvitae, ClinVar, GeneInsight COGR, MutDB, ADPKD Mutation Database, PKD1-LOVD, and PKD1-LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs547817931) as “N/A”, in the 1000 Genomes Project in 1 of 5000 chromosomes (frequency: 0.0002), the Exome Aggregation Consortium database (August 8, 2016) in 39 (1 homozygous) of 111838 chromosomes (freq. 0.0003) in the following populations: South Asian in 36 of 16250 chromosomes (freq. 0.002), European in 2 of 61142 chromosomes (freq.0.00003), and European in 1 of 8226 chromosomes (freq. 0.0001), increasing the likelihood this could be a low frequency benign variant. The p.Ala1302Ala 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. In addition, the variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In addition, this variant was identified in one individual by our laboratory as co-occurring with a pathogenic variant in PKD1 (c.12010CT, p.Gln4004X), increasing the likelihood this variant does not have clinical significance. 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. |