rs171021

Variant names:

• chr11-72606513-C-T
• rs171021
• NM_002599.5:c.235-1287G>A

Variant summary

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

The NM_002599.5(PDE2A):​c.235-1287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,082 control chromosomes in the GnomAD database, including 5,856 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 0.27 (5856 hom., cov: 32)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with paroxysmal dyskinesia or seizures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• infantile convulsions and choreoathetosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105369377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.235-1287G>A		intron_variant	Intron 3 of 30	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.235-1287G>A		intron_variant	Intron 3 of 30	1	NM_002599.5	ENSP00000334910.5

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41588 AN: 151964 Hom.: 5848 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.274 AC: 41624 AN: 152082 Hom.: 5856 Cov.: 32 AF XY: 0.280 AC XY: 20786 AN XY: 74340

African (AFR) AF: 0.205 AC: 8525 AN: 41504

American (AMR) AF: 0.276 AC: 4218 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5164

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4818

European-Finnish (FIN) AF: 0.369 AC: 3896 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19993 AN: 67978

Other (OTH) AF: 0.272 AC: 573 AN: 2108

Alfa AF: 0.277 Hom.: 1197

Bravo AF: 0.262

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.74
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs171021; hg19: chr11-72317557;