Genetic Variant PDE2A:c.-599G>A (chr11-72674681-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000542969.2(PDE2A):c.-599G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 160,224 control chromosomes in the GnomAD database, including 62,489 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 0.88 ( 59271 hom., cov: 28)

Exomes 𝑓: 0.87 ( 3218 hom. )

Consequence

PDE2A
ENST00000542969.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.476

Publications

9 publications found

Variant links:

Genes affected

PDE2A (HGNC:8777): (phosphodiesterase 2A) Enables several functions, including 3',5'-cyclic-nucleotide phosphodiesterase activity; anion binding activity; and metal ion binding activity. Involved in several processes, including cellular response to organic cyclic compound; cyclic-nucleotide-mediated signaling; and regulation of vascular permeability. Located in several cellular components, including cytosol; mitochondrial membrane; and perinuclear region of cytoplasm. Colocalizes with plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PDE2A Gene-Disease associations (from GenCC):

intellectual developmental disorder with paroxysmal dyskinesia or seizures
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
infantile convulsions and choreoathetosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PDE2A links:

Genome browser will be placed here

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 (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
PDE2A	ENST00000542969.2 link	c.-599G>A	upstream_gene_variant	4	ENSP00000443232.1	F5H5P8
PDE2A	ENST00000540380.5 link	n.-90G>A	upstream_gene_variant	4
PDE2A	ENST00000546038.1 link	n.-474G>A	upstream_gene_variant	4	ENSP00000438295.1	F5H2Z0

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133489

AN:

151662

Hom.:

59228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.852

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.889

Gnomad OTH

AF:

0.868

GnomAD4 exome

AF:

0.866

AC:

7310

AN:

8444

Hom.:

3218

AF XY:

0.865

AC XY:

3814

AN XY:

4408

show subpopulations

African (AFR)

AF:

0.965

AC:

303

AN:

314

American (AMR)

AF:

0.698

AC:

176

AN:

252

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

296

AN:

342

East Asian (EAS)

AF:

0.565

AC:

208

AN:

368

South Asian (SAS)

AF:

0.838

AC:

171

AN:

204

European-Finnish (FIN)

AF:

0.867

AC:

300

AN:

346

Middle Eastern (MID)

AF:

0.853

AC:

AN:

European-Non Finnish (NFE)

AF:

0.888

AC:

5313

AN:

5984

Other (OTH)

AF:

0.857

AC:

514

AN:

600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.880

AC:

133584

AN:

151780

Hom.:

59271

Cov.:

AF XY:

0.875

AC XY:

64920

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.948

AC:

39240

AN:

41412

American (AMR)

AF:

0.775

AC:

11816

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

2970

AN:

3468

East Asian (EAS)

AF:

0.616

AC:

3151

AN:

5112

South Asian (SAS)

AF:

0.852

AC:

4091

AN:

4802

European-Finnish (FIN)

AF:

0.857

AC:

9036

AN:

10538

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.889

AC:

60362

AN:

67898

Other (OTH)

AF:

0.866

AC:

1824

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

756

1512

2267

3023

3779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.884

Hom.:

34557

Bravo

AF:

0.874

Asia WGS

AF:

0.759

AC:

2641

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

-0.48

PromoterAI

-0.020

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over