chr11-72662452-T-G

Variant names:

• chr11-72662452-T-G
• rs3781913
• NM_002599.5:c.71+11685A>C

Variant summary

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

The NM_002599.5(PDE2A):​c.71+11685A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,870 control chromosomes in the GnomAD database, including 22,082 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 0.53 (22082 hom., cov: 32)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 42 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-AS1 (HGNC:40435): (PDE2A antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	NM_002599.5	MANE Select	c.71+11685A>C		intron	N/A	NP_002590.1
	PDE2A	NM_001146209.3		c.44+5846A>C		intron	N/A	NP_001139681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	ENST00000334456.10	TSL:1 MANE Select	c.71+11685A>C		intron	N/A	ENSP00000334910.5
	PDE2A	ENST00000540345.5	TSL:1	c.44+5846A>C		intron	N/A	ENSP00000446399.1
	PDE2A	ENST00000418754.6	TSL:2	c.71+11685A>C		intron	N/A	ENSP00000410310.2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81101 AN: 151752 Hom.: 22068 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.534 AC: 81153 AN: 151870 Hom.: 22082 Cov.: 32 AF XY: 0.521 AC XY: 38678 AN XY: 74210

African (AFR) AF: 0.573 AC: 23721 AN: 41400

American (AMR) AF: 0.454 AC: 6939 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1545 AN: 5154

South Asian (SAS) AF: 0.453 AC: 2177 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4379 AN: 10530

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38385 AN: 67916

Other (OTH) AF: 0.562 AC: 1188 AN: 2114

Alfa AF: 0.556 Hom.: 82102

Bravo AF: 0.543

Asia WGS AF: 0.397 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.78
PhyloP100		0.086
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: rs3781913; hg19: chr11-72373496;