chr11-72584862-A-T

Variant names:

• chr11-72584862-A-T
• rs452228
• NM_002599.5:c.1359+10T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002599.5(PDE2A):​c.1359+10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE2A NM_002599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 8 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.1359+10T>A		intron	N/A	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1338+10T>A		intron	N/A	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1332+10T>A		intron	N/A	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.1359+10T>A		intron	N/A	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1332+10T>A		intron	N/A	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1338+10T>A		intron	N/A	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461432 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 727056

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111612

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.44
PromoterAI		0.0071	Neutral

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: rs452228; hg19: chr11-72295906;