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

new If you want to explore the variant's impact on the transcript ENST00000542969.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542969.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE2A	ENST00000542969.2	TSL:4	c.-599G>A	upstream_gene	N/A	ENSP00000443232.1	F5H5P8
PDE2A	ENST00000540380.5	TSL:4	n.-90G>A	upstream_gene	N/A
PDE2A	ENST00000546038.1	TSL:4	n.-474G>A	upstream_gene	N/A	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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over