Genetic Variant PDE2A:p.Ala867Ala (chr11-72578247-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002599.5(PDE2A):c.2601A>G(p.Ala867Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,602,784 control chromosomes in the GnomAD database, including 199,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13553 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186375 hom. )

Consequence

PDE2A
NM_002599.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.701

Publications

22 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-72578247-T-C is Benign according to our data. Variant chr11-72578247-T-C is described in ClinVar as Benign. ClinVar VariationId is 1170426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.701 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE2A	NM_002599.5 link	c.2601A>G	p.Ala867Ala	synonymous_variant	Exon 30 of 31	ENST00000334456.10	NP_002590.1	O00408-1Q8IW54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10 link	c.2601A>G	p.Ala867Ala	synonymous_variant	Exon 30 of 31	1	NM_002599.5	ENSP00000334910.5		O00408-1

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59384

AN:

151998

Hom.:

13549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.445

GnomAD2 exomes

AF:

0.425

AC:

106896

AN:

251236

AF XY:

0.443

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.497

AC:

720584

AN:

1450666

Hom.:

186375

Cov.:

AF XY:

0.497

AC XY:

359193

AN XY:

722392

show subpopulations

African (AFR)

AF:

0.148

AC:

4935

AN:

33332

American (AMR)

AF:

0.270

AC:

12059

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12634

AN:

26056

East Asian (EAS)

AF:

0.239

AC:

9495

AN:

39678

South Asian (SAS)

AF:

0.431

AC:

37059

AN:

86042

European-Finnish (FIN)

AF:

0.404

AC:

21467

AN:

53136

Middle Eastern (MID)

AF:

0.524

AC:

3013

AN:

5754

European-Non Finnish (NFE)

AF:

0.537

AC:

591209

AN:

1101938

Other (OTH)

AF:

0.478

AC:

28713

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16993

33985

50978

67970

84963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16334

32668

49002

65336

81670

<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:

0.391

AC:

59404

AN:

152118

Hom.:

13553

Cov.:

AF XY:

0.384

AC XY:

28598

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.161

AC:

6692

AN:

41524

American (AMR)

AF:

0.355

AC:

5427

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1671

AN:

3470

East Asian (EAS)

AF:

0.244

AC:

1263

AN:

5172

South Asian (SAS)

AF:

0.407

AC:

1964

AN:

4820

European-Finnish (FIN)

AF:

0.408

AC:

4329

AN:

10602

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36306

AN:

67936

Other (OTH)

AF:

0.444

AC:

937

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1727

3453

5180

6906

8633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.488

Hom.:

73613

Bravo

AF:

0.378

Asia WGS

AF:

0.337

AC:

1173

AN:

3478

EpiCase

AF:

0.550

EpiControl

AF:

0.550

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.9

(source)

DANN

Benign

0.63

PhyloP100

-0.70

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over