chr5-77427039-G-GA

Position:

• chr5-77427039-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003719.5(PDE8B):​c.*497dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 141,952 control chromosomes in the GnomAD database, including 6,389 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6380 hom., cov: 24)
  • Exomes 𝑓: 0.28 (9 hom.)
• Consequence: PDE8B NM_003719.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

Genes affected

PDE8B (HGNC:8794): (phosphodiesterase 8B) The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

WDR41 (HGNC:25601): (WD repeat domain 41) Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-77427039-G-GA is Benign according to our data. Variant chr5-77427039-G-GA is described in ClinVar as [Benign]. Clinvar id is 354189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.*497dup		3_prime_UTR_variant	22/22	ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.*497dup		3_prime_UTR_variant	22/22	1	NM_003719.5	ENSP00000264917	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 36324 AN: 140498 Hom.: 6368 Cov.: 24

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.285 AC: 399 AN: 1402 Hom.: 9 Cov.: 0 AF XY: 0.295 AC XY: 219 AN XY: 742

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.259 AC: 36366 AN: 140550 Hom.: 6380 Cov.: 24 AF XY: 0.262 AC XY: 17790 AN XY: 68026

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.281

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Striatal Degeneration Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878934235; hg19: chr5-76722864;