11-72674681-C-T

Variant names:

• chr11-72674681-C-T
• rs341058
• ENST00000542969.2:c.-599G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542969.2(PDE2A):​c.-599G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 160,224 control chromosomes in the GnomAD database, including 62,489 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 0.88 (59271 hom., cov: 28)
  • Exomes 𝑓: 0.87 (3218 hom.)
• Consequence: PDE2A ENST00000542969.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 9 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542969.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE2A	ENST00000542969.2	TSL:4	c.-599G>A		upstream_gene	N/A	ENSP00000443232.1	F5H5P8
	PDE2A	ENST00000540380.5	TSL:4	n.-90G>A		upstream_gene	N/A
	PDE2A	ENST00000546038.1	TSL:4	n.-474G>A		upstream_gene	N/A	ENSP00000438295.1	F5H2Z0

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133489 AN: 151662 Hom.: 59228 Cov.: 28

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.868

GnomAD4 exome AF: 0.866 AC: 7310 AN: 8444 Hom.: 3218 AF XY: 0.865 AC XY: 3814 AN XY: 4408

African (AFR) AF: 0.965 AC: 303 AN: 314

American (AMR) AF: 0.698 AC: 176 AN: 252

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 296 AN: 342

East Asian (EAS) AF: 0.565 AC: 208 AN: 368

South Asian (SAS) AF: 0.838 AC: 171 AN: 204

European-Finnish (FIN) AF: 0.867 AC: 300 AN: 346

Middle Eastern (MID) AF: 0.853 AC: 29 AN: 34

European-Non Finnish (NFE) AF: 0.888 AC: 5313 AN: 5984

Other (OTH) AF: 0.857 AC: 514 AN: 600

GnomAD4 genome AF: 0.880 AC: 133584 AN: 151780 Hom.: 59271 Cov.: 28 AF XY: 0.875 AC XY: 64920 AN XY: 74164

African (AFR) AF: 0.948 AC: 39240 AN: 41412

American (AMR) AF: 0.775 AC: 11816 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2970 AN: 3468

East Asian (EAS) AF: 0.616 AC: 3151 AN: 5112

South Asian (SAS) AF: 0.852 AC: 4091 AN: 4802

European-Finnish (FIN) AF: 0.857 AC: 9036 AN: 10538

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60362 AN: 67898

Other (OTH) AF: 0.866 AC: 1824 AN: 2106

Alfa AF: 0.884 Hom.: 34557

Bravo AF: 0.874

Asia WGS AF: 0.759 AC: 2641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.59
PhyloP100		-0.48
PromoterAI		-0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs341058; hg19: chr11-72385725;