Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001357602 | SCV004453451 | likely benign | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001357602 | SCV001553116 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PAFAH1B1 p.Asn377Ser variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, MutDB, and LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs1167470350) as well as in control databases in 2 of 251488 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 1 of 30616 chromosomes (freq: 0.000033), European (Non-Finnish) in 1 of 113762 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), and Other populations. The p.Asn377 residue is conserved in mammals but not in more distantly related organisms, however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, and BLOSUM) 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, and 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. |