NM_002599.5:c.1360-20C>T

Variant names:

• chr11-72584748-G-A
• rs374262344
• NM_002599.5:c.1360-20C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_002599.5(PDE2A):​c.1360-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,612,604 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.50
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-72584748-G-A is Benign according to our data. Variant chr11-72584748-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1628483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000204 (31/152252) while in subpopulation NFE AF = 0.000397 (27/68044). AF 95% confidence interval is 0.00028. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.1360-20C>T		intron	N/A	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1339-20C>T		intron	N/A	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1333-20C>T		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.1360-20C>T		intron	N/A	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1333-20C>T		intron	N/A	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1339-20C>T		intron	N/A	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000285 AC: 71 AN: 248804 AF XY: 0.000193

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000289

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000303 AC: 442 AN: 1460352 Hom.: 1 Cov.: 34 AF XY: 0.000288 AC XY: 209 AN XY: 726464

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.000201 AC: 9 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.000267 AC: 14 AN: 52516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000366 AC: 407 AN: 1111562

Other (OTH) AF: 0.000182 AC: 11 AN: 60352

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74384

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		2.5
PromoterAI		-0.0074	Neutral
Mutation Taster		=100/0	polymorphism

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: rs374262344; hg19: chr11-72295792;