11-72612844-G-T

Variant names:

• chr11-72612844-G-T
• rs907849
• NM_002599.5:c.145-4093C>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.145-4093C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,122 control chromosomes in the GnomAD database, including 52,478 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 0.83 (52478 hom., cov: 31)
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE2A	NM_002599.5	c.145-4093C>A		intron_variant	Intron 2 of 30	ENST00000334456.10	NP_002590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE2A	ENST00000334456.10	c.145-4093C>A		intron_variant	Intron 2 of 30	1	NM_002599.5	ENSP00000334910.5

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126033 AN: 152004 Hom.: 52423 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.829 AC: 126141 AN: 152122 Hom.: 52478 Cov.: 31 AF XY: 0.829 AC XY: 61674 AN XY: 74374

African (AFR) AF: 0.881 AC: 36561 AN: 41488

American (AMR) AF: 0.831 AC: 12694 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2668 AN: 3470

East Asian (EAS) AF: 0.925 AC: 4782 AN: 5172

South Asian (SAS) AF: 0.868 AC: 4189 AN: 4826

European-Finnish (FIN) AF: 0.792 AC: 8393 AN: 10594

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54053 AN: 67986

Other (OTH) AF: 0.840 AC: 1774 AN: 2112

Alfa AF: 0.816 Hom.: 6542

Bravo AF: 0.833

Asia WGS AF: 0.895 AC: 3113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.65
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs907849; hg19: chr11-72323888;