Submissions for variant NM_003719.5(PDE8B):c.125G>C (p.Gly42Ala)

gnomAD frequency: 0.00001  dbSNP: rs886060754

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000405028	SCV000458199	uncertain significance	Autosomal dominant striatal neurodegeneration type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987519	SCV004803586	uncertain significance	not specified	2024-01-22	criteria provided, single submitter	clinical testing	Variant summary: PDE8B c.125G>C (p.Gly42Ala) results in a non-conservative amino acid change located in the 3'5'-cyclic nucleotide phosphodiesterase PDE8 (IPR013938) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 141348 control chromosomes, predominantly at a frequency of 8.2e-05 within the Latino subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.125G>C in individuals affected with PDE8B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 354146). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV004649140	SCV005151618	uncertain significance	Inborn genetic diseases	2024-05-02	criteria provided, single submitter	clinical testing	The c.125G>C (p.G42A) alteration is located in exon 1 (coding exon 1) of the PDE8B gene. This alteration results from a G to C substitution at nucleotide position 125, causing the glycine (G) at amino acid position 42 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.