Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000277568 | SCV000384164 | uncertain significance | Fraser syndrome 2 | 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. |
Knight Diagnostic Laboratories, |
RCV000277568 | SCV001448892 | uncertain significance | Fraser syndrome 2 | 2019-09-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001701947 | SCV002513752 | uncertain significance | not provided | 2022-05-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002480124 | SCV002787994 | uncertain significance | Isolated cryptophthalmia; Fraser syndrome 2 | 2022-05-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001701947 | SCV003283434 | uncertain significance | not provided | 2022-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 811 of the FREM2 protein (p.Gly811Glu). This variant is present in population databases (rs147293913, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with FREM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 311958). 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: "Probably 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. |
Prevention |
RCV003430827 | SCV004117795 | uncertain significance | FREM2-related condition | 2023-07-21 | criteria provided, single submitter | clinical testing | The FREM2 c.2432G>A variant is predicted to result in the amino acid substitution p.Gly811Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-39263913-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Genome Diagnostics Laboratory, |
RCV001701947 | SCV001930923 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001701947 | SCV001963944 | uncertain significance | not provided | no assertion criteria provided | clinical testing |