ClinVar Miner

Submissions for variant NM_207361.6(FREM2):c.4150C>T (p.His1384Tyr)

gnomAD frequency: 0.00012  dbSNP: rs192340937
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV002251148 SCV002521601 uncertain significance Fraser syndrome 2 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.017%). Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.67; 3Cnet: 0.10). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV002502057 SCV002780789 uncertain significance Isolated cryptophthalmia; Fraser syndrome 2 2022-04-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003094083 SCV003265416 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1384 of the FREM2 protein (p.His1384Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1687466). 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.
GeneDx RCV003094083 SCV004036912 uncertain significance not provided 2023-03-20 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
PreventionGenetics, part of Exact Sciences RCV003395433 SCV004119953 uncertain significance FREM2-related disorder 2023-04-12 criteria provided, single submitter clinical testing The FREM2 c.4150C>T variant is predicted to result in the amino acid substitution p.His1384Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.14% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-39265631-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.