Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Pathology and Laboratory Medicine, |
RCV000500680 | SCV000592751 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ala920Gly variant was not identified in the literature nor was it identified in the dbSNP, Clinvitae, ClinVar, GeneInsight COGR, MutDB, ADPKD Mutation Database, PKD1-LOVD, PKD1-LOVD 3.0, NHLBI GO Exome Sequencing Project and Exome Aggregation Consortium (August 8, 2016) databases. The p.Ala920 residue is not conserved in mammals and 1 out of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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 from our laboratory as co-occurring with a pathogenic variant in PKD1 (c.7137C>G, p.Tyr2379X), 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. |