Submissions for variant NM_002732.4(PRKACG):c.239T>C (p.Val80Ala)

gnomAD frequency: 0.00135  dbSNP: rs148063597

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV001820530	SCV002070072	uncertain significance	not specified	2021-11-22	criteria provided, single submitter	clinical testing	DNA sequence analysis of the PRKACG gene demonstrated a sequence change, c.239T>C, in exon 1 that results in an amino acid change, p.Val80Ala. This sequence change has been described in the gnomAD database with a frequency of 0.48% in the African/African American subpopulation (dbSNP rs148063597). The p.Val80Ala change affects a highly conserved amino acid residue located in a domain of the PRKACG protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Val80Ala substitution. This sequence change does not appear to have been previously described in individuals with PRKACG-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Val80Ala change remains unknown at this time.
PreventionGenetics, part of Exact Sciences	RCV003941162	SCV004749133	likely benign	PRKACG-related disorder	2021-01-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).