Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000903398 | SCV001047864 | likely benign | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000903398 | SCV001549809 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The POLR1A p.Pro673Ala variant was not identified in the literature but was identified in dbSNP (ID: rs191928354), ClinVar (classified as likely benign by Invitae), and LOVD 3.0. The variant was identified in control databases in 150 of 280812 chromosomes at a frequency of 0.0005342 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 127 of 24200 chromosomes (freq: 0.005248), Latino in 19 of 35364 chromosomes (freq: 0.000537), Other in 2 of 7144 chromosomes (freq: 0.00028) and European (non-Finnish) in 2 of 128578 chromosomes (freq: 0.000016), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Pro673 residue is conserved across mammals and other organisms, and four out of five 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. |