chr11-72584649-T-C

Variant names:

• chr11-72584649-T-C
• rs1855880808
• NM_002599.5:c.1439A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 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
• Publications: 2 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: Likely_pathogenic. The variant received 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 VariationId is 995828.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1439A>G	p.Asp480Gly	missense	Exon 18 of 31	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1418A>G	p.Asp473Gly	missense	Exon 17 of 30	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1412A>G	p.Asp471Gly	missense	Exon 19 of 32	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.1439A>G	p.Asp480Gly	missense	Exon 18 of 31	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1412A>G	p.Asp471Gly	missense	Exon 19 of 32	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1418A>G	p.Asp473Gly	missense	Exon 17 of 30	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual developmental disorder with paroxysmal dyskinesia or seizures (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	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
PromoterAI		-0.077	Neutral
Varity_R		0.78
gMVP		0.99
Mutation Taster		=2/98	disease causing (ClinVar)

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: rs1855880808; hg19: chr11-72295693;