ClinVar Miner

Submissions for variant NM_207361.6(FREM2):c.383C>T (p.Pro128Leu)

gnomAD frequency: 0.00004  dbSNP: rs114864077
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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 RCV001111817 SCV001269418 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002555080 SCV003481864 uncertain significance not provided 2022-06-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 128 of the FREM2 protein (p.Pro128Leu). This variant is present in population databases (rs114864077, gnomAD 0.2%). 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: 882275). 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: "Benign"; 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.
Revvity Omics, Revvity RCV002555080 SCV003828376 uncertain significance not provided 2021-07-26 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003396752 SCV004104756 uncertain significance FREM2-related disorder 2023-05-24 criteria provided, single submitter clinical testing The FREM2 c.383C>T variant is predicted to result in the amino acid substitution p.Pro128Leu. To our knowledge, this variant has not been reported in individuals with FREM2-associated phenotypes in the literature. This variant is reported in 0.19% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-39261864-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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