11-72662993-C-T

Variant names:

• chr11-72662993-C-T
• rs11235559
• NM_002599.5:c.71+11144G>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.71+11144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,982 control chromosomes in the GnomAD database, including 14,785 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 0.42 (14785 hom., cov: 32)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	NM_002599.5	MANE Select	c.71+11144G>A		intron	N/A	NP_002590.1
	PDE2A	NM_001146209.3		c.44+5305G>A		intron	N/A	NP_001139681.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	ENST00000334456.10	TSL:1 MANE Select	c.71+11144G>A		intron	N/A	ENSP00000334910.5
	PDE2A	ENST00000540345.5	TSL:1	c.44+5305G>A		intron	N/A	ENSP00000446399.1
	PDE2A	ENST00000418754.6	TSL:2	c.71+11144G>A		intron	N/A	ENSP00000410310.2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63165 AN: 151864 Hom.: 14790 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.416 AC: 63166 AN: 151982 Hom.: 14785 Cov.: 32 AF XY: 0.405 AC XY: 30096 AN XY: 74252

African (AFR) AF: 0.210 AC: 8713 AN: 41426

American (AMR) AF: 0.404 AC: 6166 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1893 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1536 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4812

European-Finnish (FIN) AF: 0.389 AC: 4105 AN: 10544

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36959 AN: 67992

Other (OTH) AF: 0.486 AC: 1023 AN: 2104

Alfa AF: 0.473 Hom.: 9553

Bravo AF: 0.414

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		0.13
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: rs11235559; hg19: chr11-72374037;