11-72584649-T-C

Position:

• chr11-72584649-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_002599.5(PDE2A):​c.1439A>G​(p.Asp480Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDE2A NM_002599.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.81

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

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957
• PP5: Variant 11-72584649-T-C is Pathogenic according to our data. Variant chr11-72584649-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 995828.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.1439A>G	p.Asp480Gly	missense_variant	18/31	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.1439A>G	p.Asp480Gly	missense_variant	18/31	1	NM_002599.5	ENSP00000334910.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder with paroxysmal dyskinesia or seizures Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.;.;.;T;.;D
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.9	H;.;.;.;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.4	D;D;.;D;D;D;D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0040	D;D;.;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;.
Polyphen		1.0	D;.;.;.;D;.;.
Vest4		0.96
MutPred		0.83		Loss of phosphorylation at Y482 (P = 0.1148);.;.;.;.;.;.;
MVP		0.90
MPC		2.8
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.99

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: rs1855880808; hg19: chr11-72295693;