rs452228

Variant names:

• chr11-72584862-A-G
• rs452228
• NM_002599.5:c.1359+10T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-72584862-A-G
• chr11-72584862-A-C
• chr11-72584862-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002599.5(PDE2A):​c.1359+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,613,704 control chromosomes in the GnomAD database, including 800,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73113 hom., cov: 31)
  • Exomes 𝑓: 1.0 (727823 hom.)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.438
• Publications: 8 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-AS2 (HGNC:40434): (PDE2A antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-72584862-A-G is Benign according to our data. Variant chr11-72584862-A-G is described in ClinVar as Benign. ClinVar VariationId is 1165285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 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.1359+10T>C		intron	N/A	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1338+10T>C		intron	N/A	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1332+10T>C		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.1359+10T>C		intron	N/A	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1332+10T>C		intron	N/A	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1338+10T>C		intron	N/A	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149037 AN: 152158 Hom.: 73056 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

GnomAD2 exomes AF: 0.995 AC: 250097 AN: 251392 AF XY: 0.996

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 1458460 AN: 1461428 Hom.: 727823 Cov.: 43 AF XY: 0.998 AC XY: 725793 AN XY: 727054

African (AFR) AF: 0.929 AC: 31082 AN: 33462

American (AMR) AF: 0.996 AC: 44544 AN: 44720

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26132 AN: 26132

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39698

South Asian (SAS) AF: 1.00 AC: 86239 AN: 86250

European-Finnish (FIN) AF: 1.00 AC: 53408 AN: 53408

Middle Eastern (MID) AF: 0.999 AC: 5759 AN: 5766

European-Non Finnish (NFE) AF: 1.00 AC: 1111502 AN: 1111612

Other (OTH) AF: 0.995 AC: 60096 AN: 60380

GnomAD4 genome AF: 0.979 AC: 149152 AN: 152276 Hom.: 73113 Cov.: 31 AF XY: 0.980 AC XY: 72966 AN XY: 74448

African (AFR) AF: 0.929 AC: 38592 AN: 41554

American (AMR) AF: 0.993 AC: 15192 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5158

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68014 AN: 68028

Other (OTH) AF: 0.985 AC: 2081 AN: 2112

Alfa AF: 0.987 Hom.: 37422

Bravo AF: 0.977

Asia WGS AF: 0.997 AC: 3467 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.44
PromoterAI		0.017	Neutral
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: rs452228; hg19: chr11-72295906;