rs138160928

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

The FGD4 c.1366C>A; p.Pro456Thr variant (rs138160928), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 188187). This variant is found in the non-Finnish European population with an overall allele frequency of 0.27% (344/129172 alleles, including one homozygote) in the Genome Aggregation Database. The proline at codon 456 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.717). However, due to limited information, the clinical significance of the p.Pro456Thr variant is uncertain at this time.