Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001137254 | SCV001297179 | uncertain significance | Periventricular heterotopia with microcephaly, autosomal recessive | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Genetic Services Laboratory, |
RCV001819841 | SCV002070396 | uncertain significance | not specified | 2020-09-14 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ARFGEF2 gene demonstrated a sequence change, c.3274C>T, in exon 25 that results in an amino acid change, p.Arg1092Cys. This sequence change does not appear to have been previously described in patients with ARFGEF2-related disorders and has been described in the gnomAD database in seven individuals with an overall population frequency of 0.003% (dbSNP rs144190029). The p.Arg1092Cys change affects a highly conserved amino acid residue located in a domain of the ARFGEF2 protein that is not known to be functional. The p.Arg1092Cys substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg1092Cys change remains unknown at this time. |
Ambry Genetics | RCV002556918 | SCV003611277 | uncertain significance | Inborn genetic diseases | 2022-05-14 | criteria provided, single submitter | clinical testing | The c.3274C>T (p.R1092C) alteration is located in exon 25 (coding exon 25) of the ARFGEF2 gene. This alteration results from a C to T substitution at nucleotide position 3274, causing the arginine (R) at amino acid position 1092 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |