11-72577393-A-T

Position:

chr11-72577393-A-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_002599.5(PDE2A):c.2817T>A(p.Asp939Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,612,562 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 43 hom. )

Consequence

PDE2A
NM_002599.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.999

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PDE2A. . Gene score misZ 4.056 (greater than the threshold 3.09). Trascript score misZ 3.8645 (greater than threshold 3.09). GenCC has associacion of gene with intellectual developmental disorder with paroxysmal dyskinesia or seizures, infantile convulsions and choreoathetosis.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014609694).

BP6

Variant 11-72577393-A-T is Benign according to our data. Variant chr11-72577393-A-T is described in ClinVar as [Benign]. Clinvar id is 1168004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00305 (464/152306) while in subpopulation AMR AF= 0.0265 (406/15308). AF 95% confidence interval is 0.0244. There are 10 homozygotes in gnomad4. There are 268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE2A	NM_002599.5 linkuse as main transcript	c.2817T>A	p.Asp939Glu	missense_variant	31/31	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10 linkuse as main transcript	c.2817T>A	p.Asp939Glu	missense_variant	31/31	1	NM_002599.5	ENSP00000334910	A1	O00408-1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00578

AC:

1445

AN:

250016

Hom.:

AF XY:

0.00435

AC XY:

588

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0392

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00127

AC:

1858

AN:

1460256

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

799

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00305

AC:

464

AN:

152306

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000658

Hom.:

Bravo

AF:

0.00492

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00421

AC:

511

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.0

DANN

Benign

0.92

DEOGEN2

Benign

0.082

T;.;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.72

T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.11

N;N;.;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.39

T;T;.;T;T;T

Sift4G

Benign

0.64

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;B;.

Vest4

0.044

MutPred

0.18

Gain of disorder (P = 0.1295);.;.;.;.;.;

MVP

0.54

MPC

1.2

ClinPred

0.0029

GERP RS

-9.4

Varity_R

0.046

gMVP

0.13

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over