ClinVar Miner

Submissions for variant NM_207361.6(FREM2):c.4823G>A (p.Gly1608Asp)

gnomAD frequency: 0.00004  dbSNP: rs767651775
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001109794 SCV001267165 uncertain significance Fraser syndrome 2 2018-01-12 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002558100 SCV003480243 uncertain significance not provided 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1608 of the FREM2 protein (p.Gly1608Asp). This variant is present in population databases (rs767651775, gnomAD 0.01%). 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: 881065). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FREM2 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002556152 SCV003536363 uncertain significance Inborn genetic diseases 2021-10-27 criteria provided, single submitter clinical testing The c.4823G>A (p.G1608D) alteration is located in exon 1 (coding exon 1) of the FREM2 gene. This alteration results from a G to A substitution at nucleotide position 4823, causing the glycine (G) at amino acid position 1608 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005012559 SCV005634731 uncertain significance Isolated cryptophthalmia; Fraser syndrome 2 2024-04-12 criteria provided, single submitter clinical testing

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