Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002548517 | SCV003568142 | uncertain significance | Inborn genetic diseases | 2021-08-02 | criteria provided, single submitter | clinical testing | The c.2191T>C (p.W731R) alteration is located in exon 17 (coding exon 15) of the FGD4 gene. This alteration results from a T to C substitution at nucleotide position 2191, causing the tryptophan (W) at amino acid position 731 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV001357146 | SCV001552515 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The FGD4 p.Trp843Arg variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs980987965) and in control databases in 1 of 251206 chromosomes at a frequency of 0.000003981 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 1 of 113502 chromosomes (freq: 0.000009), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Trp843 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |