rs3781931

Variant names:

• chr11-72616161-C-T
• rs3781931
• NM_002599.5:c.145-7410G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002599.5(PDE2A):​c.145-7410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,186 control chromosomes in the GnomAD database, including 1,585 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 0.14 (1585 hom., cov: 32)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 9 publications found

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

LOC105369377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.145-7410G>A		intron_variant	Intron 2 of 30	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.145-7410G>A		intron_variant	Intron 2 of 30	1	NM_002599.5	ENSP00000334910.5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20918 AN: 152068 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20932 AN: 152186 Hom.: 1585 Cov.: 32 AF XY: 0.142 AC XY: 10544 AN XY: 74416

African (AFR) AF: 0.0777 AC: 3228 AN: 41528

American (AMR) AF: 0.128 AC: 1962 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.182 AC: 942 AN: 5166

South Asian (SAS) AF: 0.199 AC: 958 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10582

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10539 AN: 68002

Other (OTH) AF: 0.158 AC: 334 AN: 2116

Alfa AF: 0.141 Hom.: 622

Bravo AF: 0.127

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781931; hg19: chr11-72327205;