Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000348468 | SCV000337432 | uncertain significance | not provided | 2015-11-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000348468 | SCV001783402 | pathogenic | not provided | 2021-04-09 | criteria provided, single submitter | clinical testing | Published functional studies suggest a damaging effect resulting in impaired function of FREM2 in cell adhesion (Yu et al., 2018); 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: 29688405, 30802441) |
Invitae | RCV000348468 | SCV004538903 | pathogenic | not provided | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2167 of the FREM2 protein (p.Arg2167Trp). This variant is present in population databases (rs114837786, gnomAD 0.05%). This missense change has been observed in individual(s) with cryptophthalmos (PMID: 29688405, 30802441). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 284704). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FREM2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects FREM2 function (PMID: 29688405, 30802441). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000767220 | SCV000897762 | pathogenic | Isolated cryptophthalmia | 2019-12-18 | no assertion criteria provided | literature only | |
OMIM | RCV000767221 | SCV000897765 | pathogenic | Fraser syndrome 2 | 2019-12-18 | no assertion criteria provided | literature only |