Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000488371 | SCV000231269 | uncertain significance | not provided | 2015-01-22 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000384240 | SCV000451246 | uncertain significance | Fraser syndrome 1 | 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. |
Ce |
RCV000488371 | SCV000575411 | uncertain significance | not provided | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000488371 | SCV000616729 | uncertain significance | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | Observed in the presence of a second FRAS1 variant, as identified by whole exome sequencing, in an individual with acinar dysplasia; however, this individual was also found to have a variant in a different gene that may be influencing the phenotype (Karolak et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30639323) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824664 | SCV002074390 | likely benign | not specified | 2022-01-21 | criteria provided, single submitter | clinical testing | Variant summary: FRAS1 c.7039G>T (p.Val2347Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 248778 control chromosomes, predominantly at a frequency of 0.0025 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in FRAS1 causing Cryptophthalmos Syndrome phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.7039G>T has been reported in the literature with an unknown inheritance pattern in an individual affected with lung hypoplasia presenting as marked variation with acinar dysplasia ranging to near normal (example, Karolak_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Fraser/Cryptophthalmos Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Invitae | RCV000488371 | SCV002437582 | likely benign | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000384240 | SCV003828351 | uncertain significance | Fraser syndrome 1 | 2022-09-19 | criteria provided, single submitter | clinical testing |