Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000559788 | SCV000655233 | uncertain significance | Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with cysteine at codon 1400 of the GLI2 protein (p.Gly1400Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs143914758, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals affected with GLI2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Eurofins Ntd Llc |
RCV000592191 | SCV000704925 | uncertain significance | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000592191 | SCV001152395 | uncertain significance | not provided | 2018-12-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001131582 | SCV001291213 | likely benign | Holoprosencephaly 9 | 2017-09-14 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |