Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001355399 | SCV002050059 | likely benign | not provided | 2020-12-02 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355399 | SCV001550275 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PLEKHG5 p.Gly32Ser variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs554689677) and was identified in control databases in 74 of 74640 chromosomes at a frequency of 0.0009914 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 54 of 30898 chromosomes (freq: 0.001748), Latino in 12 of 8790 chromosomes (freq: 0.001365), African in 4 of 9128 chromosomes (freq: 0.000438), Other in 1 of 2360 chromosomes (freq: 0.000424), South Asian in 2 of 10680 chromosomes (freq: 0.000187) and European (Finnish) in 1 of 6326 chromosomes (freq: 0.000158), but was not observed in the Ashkenazi Jewish, or East Asian populations. The p.Gly32 residue is conserved across mammals and other organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out 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. |