PDE2A p.Asp409Glu

Variant names:

• chr11-72585430-G-T
• NM_002599.5:c.1227C>A
• PDE2A p.Asp409Glu

Your query was ambiguous. Multiple possible variants found:

• chr11-72585430-G-T
• chr11-72585430-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002599.5(PDE2A):​c.1227C>A​(p.Asp409Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE2A NM_002599.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

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.1227C>A	p.Asp409Glu	missense	Exon 16 of 31	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1206C>A	p.Asp402Glu	missense	Exon 15 of 30	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1200C>A	p.Asp400Glu	missense	Exon 17 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.1227C>A	p.Asp409Glu	missense	Exon 16 of 31	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1200C>A	p.Asp400Glu	missense	Exon 17 of 32	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1206C>A	p.Asp402Glu	missense	Exon 15 of 30	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	7.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.55
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.50
Sift	Benign	0.094	T
Sift4G	Benign	0.068	T
Varity_R		0.17
gMVP		0.54
Mutation Taster		=54/46	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-72296474;