Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001121262 | SCV001279843 | uncertain significance | Bilateral frontoparietal polymicrogyria | 2018-01-13 | criteria provided, single submitter | clinical testing | 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. |
Genetic Services Laboratory, |
RCV001819832 | SCV002070258 | uncertain significance | not specified | 2020-06-05 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ADGRG1 gene demonstrated a sequence change, c.1805A>G, in exon 14 that results in an amino acid change, p.His602Arg. This sequence change does not appear to have been previously described in patients with ADGRG1-related disorders and has been described in the gnomAD database with a low population frequency of 0.0018% (dbSNP rs576843318). The p.His602Arg change affects a moderately conserved amino acid residue located in a domain of the ADGRG1 protein that is known to be functional. The p.His602Arg substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.His602Arg change remains unknown at this time. |