Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001266541 | SCV001444717 | uncertain significance | Inborn genetic diseases | 2022-08-16 | criteria provided, single submitter | clinical testing | The c.1480T>C (p.W494R) alteration is located in exon 15 (coding exon 13) of the PRMT7 gene. This alteration results from a T to C substitution at nucleotide position 1480, causing the tryptophan (W) at amino acid position 494 to be replaced by an arginine (R). Based on data from gnomAD, the C allele has an overall frequency of 0.0008% (2/250826) total alleles studied. The highest observed frequency was 0.003% (1/34578) of Latino alleles. The c.1480T>C (p.W494R) alteration has been reported in trans with a splice alteration in two siblings with mild intellectual disability, short stature, obesity, and brachydactyly (Akawi, 2015). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001855017 | SCV002310602 | likely pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 266021). This missense change has been observed in individual(s) with short stature, brachydactyly, intellectual developmental disability, and seizures (SBIDDS) (PMID: 26437029, 28902392). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs751670999, gnomAD 0.003%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 494 of the PRMT7 protein (p.Trp494Arg). |
| OMIM | RCV000256434 | SCV000323182 | pathogenic | Short stature-brachydactyly-obesity-global developmental delay syndrome | 2020-07-03 | no assertion criteria provided | literature only |