Genetic Variant PDE8A:c.-190+236G>A (chr15-84980738-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001243137.2(PDE8A):c.-31+53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,276 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1309 hom., cov: 33)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

PDE8A
NM_001243137.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.722

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243137.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	NM_001243137.2		c.-31+53G>A		intron	N/A	NP_001230066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000310298.8	TSL:1	c.-190+236G>A		intron	N/A	ENSP00000311453.4
	PDE8A	ENST00000557957.5	TSL:2	c.-31+53G>A		intron	N/A	ENSP00000453808.1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17293

AN:

152080

Hom.:

1312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0395

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.122

AC:

AN:

Hom.:

AF XY:

0.121

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.129

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.114

AC:

17286

AN:

152202

Hom.:

1309

Cov.:

AF XY:

0.117

AC XY:

8705

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0250

AC:

1039

AN:

41562

American (AMR)

AF:

0.101

AC:

1552

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

678

AN:

3470

East Asian (EAS)

AF:

0.0394

AC:

204

AN:

5180

South Asian (SAS)

AF:

0.105

AC:

504

AN:

4810

European-Finnish (FIN)

AF:

0.212

AC:

2243

AN:

10584

Middle Eastern (MID)

AF:

0.217

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.154

AC:

10441

AN:

67980

Other (OTH)

AF:

0.119

AC:

251

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

769

1537

2306

3074

3843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.137

Hom.:

2029

Bravo

AF:

0.102

Asia WGS

AF:

0.0610

AC:

211

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.8

(source)

DANN

Benign

0.86

PhyloP100

0.72

PromoterAI

-0.079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over