chr11-72584924-T-C

Position:

• chr11-72584924-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002599.5(PDE2A):​c.1307A>G​(p.Asp436Gly) variant causes a missense change. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDE2A NM_002599.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.1307A>G	p.Asp436Gly	missense_variant	17/31	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.1307A>G	p.Asp436Gly	missense_variant	17/31	1	NM_002599.5	ENSP00000334910.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1307A>G (p.D436G) alteration is located in exon 17 (coding exon 17) of the PDE2A gene. This alteration results from a A to G substitution at nucleotide position 1307, causing the aspartic acid (D) at amino acid position 436 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.;.;.;T;.;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.4	M;.;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.8	D;D;.;D;D;D;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0050	D;D;.;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;.
Polyphen		0.99	D;.;.;.;D;.;.
Vest4		0.77
MutPred		0.62		Gain of sheet (P = 0.1208);.;.;.;.;.;.;
MVP		0.81
MPC		2.8
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.71
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-72295968;