Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014752.3(SPCS2):āc.40A>Cā(p.Ser14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14G) has been classified as Likely benign.
SPCS2 (HGNC:28962): (signal peptidase complex subunit 2) Predicted to enable peptidase activity. Predicted to be involved in protein targeting to ER and signal peptide processing. Predicted to be located in endoplasmic reticulum membrane. Predicted to be part of signal peptidase complex. [provided by Alliance of Genome Resources, Apr 2022]
XRRA1 (HGNC:18868): (X-ray radiation resistance associated 1) Involved in response to X-ray. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]
Loss of glycosylation at S14 (P = 9e-04);Loss of glycosylation at S14 (P = 9e-04);Loss of glycosylation at S14 (P = 9e-04);Loss of glycosylation at S14 (P = 9e-04);