11-72577393-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.999

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PDE2A
• 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_single_submitter, 1 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 GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE2A	NM_002599.5	c.2817T>A	p.Asp939Glu	missense_variant	31/31	ENST00000334456.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE2A	ENST00000334456.10	c.2817T>A	p.Asp939Glu	missense_variant	31/31	1	NM_002599.5	A1

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 462 AN: 152188 Hom.: 10 Cov.: 33

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.: 31 AF XY: 0.00435 AC XY: 588 AN XY: 135222

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.: 43 Cov.: 30 AF XY: 0.00110 AC XY: 799 AN XY: 726450

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.: 10 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74474

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.: 0

Bravo AF: 0.00492

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00421 AC: 511

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.60	T
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	N
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	T
MutationAssessor	Benign	0.81	L;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.42	T
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	T
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

Other links and lift over

dbSNP: rs142967171; hg19: chr11-72288437;