chr11-72650269-T-C

Variant names:

• chr11-72650269-T-C
• rs163692
• NM_002599.5:c.72-7943A>G

Variant summary

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

The NM_002599.5(PDE2A):​c.72-7943A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 151,908 control chromosomes in the GnomAD database, including 46,012 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 0.77 (46012 hom., cov: 30)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23
• Publications: 1 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 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.72-7943A>G		intron	N/A	NP_002590.1	O00408-1
	PDE2A	NM_001146209.3		c.45-7943A>G		intron	N/A	NP_001139681.1	O00408-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	ENST00000334456.10	TSL:1 MANE Select	c.72-7943A>G		intron	N/A	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.45-7943A>G		intron	N/A	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000418754.6	TSL:2	c.72-7943A>G		intron	N/A	ENSP00000410310.2	E9PEF1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117439 AN: 151790 Hom.: 45999 Cov.: 30

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.773 AC: 117486 AN: 151908 Hom.: 46012 Cov.: 30 AF XY: 0.767 AC XY: 56925 AN XY: 74242

African (AFR) AF: 0.757 AC: 31350 AN: 41404

American (AMR) AF: 0.657 AC: 10021 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2751 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2484 AN: 5128

South Asian (SAS) AF: 0.786 AC: 3784 AN: 4812

European-Finnish (FIN) AF: 0.787 AC: 8312 AN: 10564

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56074 AN: 67958

Other (OTH) AF: 0.772 AC: 1625 AN: 2104

Alfa AF: 0.790 Hom.: 5930

Bravo AF: 0.760

Asia WGS AF: 0.639 AC: 2226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.20
PhyloP100		-4.2
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: rs163692; hg19: chr11-72361313;