ClinVar Miner

Submissions for variant NM_025074.7(FRAS1):c.7039G>T (p.Val2347Phe)

gnomAD frequency: 0.00131  dbSNP: rs201369510
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000488371 SCV000231269 uncertain significance not provided 2015-01-22 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina 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.
CeGaT Center for Human Genetics Tuebingen RCV000488371 SCV000575411 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing
GeneDx 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, LabCorp 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, Revvity Omics RCV000384240 SCV003828351 uncertain significance Fraser syndrome 1 2022-09-19 criteria provided, single submitter clinical testing

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