11-72669208-T-C

Variant names:

• chr11-72669208-T-C
• rs189332
• NM_002599.5:c.71+4929A>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.71+4929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 153,046 control chromosomes in the GnomAD database, including 15,145 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 (15005 hom., cov: 32)
  • Exomes 𝑓: 0.52 (140 hom.)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 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+4929A>G		intron	N/A	NP_002590.1
	PDE2A	NM_001146209.3		c.-284A>G		upstream_gene	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+4929A>G		intron	N/A	ENSP00000334910.5
	PDE2A	ENST00000418754.6	TSL:2	c.71+4929A>G		intron	N/A	ENSP00000410310.2
	PDE2A	ENST00000542969.2	TSL:4	c.-55+4929A>G		intron	N/A	ENSP00000443232.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64245 AN: 151930 Hom.: 15010 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.516 AC: 515 AN: 998 Hom.: 140 AF XY: 0.498 AC XY: 264 AN XY: 530

African (AFR) AF: 0.111 AC: 2 AN: 18

American (AMR) AF: 0.0714 AC: 1 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.364 AC: 8 AN: 22

European-Finnish (FIN) AF: 0.400 AC: 40 AN: 100

Middle Eastern (MID) AF: 0.546 AC: 95 AN: 174

European-Non Finnish (NFE) AF: 0.548 AC: 351 AN: 640

Other (OTH) AF: 0.607 AC: 17 AN: 28

GnomAD4 genome AF: 0.423 AC: 64243 AN: 152048 Hom.: 15005 Cov.: 32 AF XY: 0.411 AC XY: 30566 AN XY: 74302

African (AFR) AF: 0.237 AC: 9820 AN: 41478

American (AMR) AF: 0.405 AC: 6186 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1909 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5164

South Asian (SAS) AF: 0.368 AC: 1772 AN: 4814

European-Finnish (FIN) AF: 0.387 AC: 4081 AN: 10546

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37053 AN: 67982

Other (OTH) AF: 0.498 AC: 1052 AN: 2112

Alfa AF: 0.489 Hom.: 8975

Bravo AF: 0.423

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.76
PhyloP100		0.84
PromoterAI		-0.0085	Neutral
Mutation Taster		=99/1	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: rs189332; hg19: chr11-72380252;