11-72669208-T-C

Position:

• chr11-72669208-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.71+4929A>G		intron_variant		ENST00000334456.10	NP_002590.1
PDE2A-AS1	XR_001748293.2	n.216-622T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.71+4929A>G		intron_variant		1	NM_002599.5	ENSP00000334910.5

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

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.607

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.498

Alfa AF: 0.487 Hom.: 7826

Bravo AF: 0.423

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs189332; hg19: chr11-72380252;