Variant rs62019510 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002605.3(PDE8A):c.1202A>G(p.Asn401Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0298 in 1,611,760 control chromosomes in the GnomAD database, including 869 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.022 ( 58 hom., cov: 32)

Exomes 𝑓: 0.031 ( 811 hom. )

Consequence

PDE8A
NM_002605.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Variant links:

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

PDE8A links:

PDE8A (HGNC:):

PDE8A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050416887).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0216 (3294/152326) while in subpopulation NFE AF= 0.0353 (2402/68028). AF 95% confidence interval is 0.0341. There are 58 homozygotes in gnomad4. There are 1508 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE8A	NM_002605.3 linkuse as main transcript	c.1202A>G	p.Asn401Ser	missense_variant	14/22	ENST00000394553.6	NP_002596.1	O60658-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6 linkuse as main transcript	c.1202A>G	p.Asn401Ser	missense_variant	14/22	1	NM_002605.3	ENSP00000378056.1		O60658-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3293

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0243

AC:

6067

AN:

249982

Hom.:

120

AF XY:

0.0246

AC XY:

3321

AN XY:

135046

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0439

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.0149

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0306

AC:

44683

AN:

1459434

Hom.:

811

Cov.:

AF XY:

0.0305

AC XY:

22120

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.00539

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.0403

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0347

Gnomad4 OTH exome

AF:

0.0288

GnomAD4 genome

AF:

0.0216

AC:

3294

AN:

152326

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1508

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00548

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.0171

Gnomad4 NFE

AF:

0.0353

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0326

Hom.:

130

Bravo

AF:

0.0208

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0378

AC:

325

ExAC

AF:

0.0238

AC:

2894

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0340

EpiControl

AF:

0.0365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D;.;D

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.5

D;D;D;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.11

B;.;B;P

Vest4

0.12

MPC

0.16

ClinPred

0.039

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over