chr11-72584690-C-T

Variant names:

• chr11-72584690-C-T
• rs150054293
• NM_002599.5:c.1398G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002599.5(PDE2A):​c.1398G>A​(p.Ala466Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,613,372 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (14 hom.)
• Consequence: PDE2A NM_002599.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-72584690-C-T is Benign according to our data. Variant chr11-72584690-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1335080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00205 (312/152304) while in subpopulation NFE AF = 0.00348 (237/68016). AF 95% confidence interval is 0.00312. There are 2 homozygotes in GnomAd4. There are 148 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

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.1398G>A	p.Ala466Ala	synonymous	Exon 18 of 31	NP_002590.1	O00408-1
	PDE2A	NM_001143839.4		c.1377G>A	p.Ala459Ala	synonymous	Exon 17 of 30	NP_001137311.1	O00408-3
	PDE2A	NM_001146209.3		c.1371G>A	p.Ala457Ala	synonymous	Exon 19 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.1398G>A	p.Ala466Ala	synonymous	Exon 18 of 31	ENSP00000334910.5	O00408-1
	PDE2A	ENST00000540345.5	TSL:1	c.1371G>A	p.Ala457Ala	synonymous	Exon 19 of 32	ENSP00000446399.1	O00408-4
	PDE2A	ENST00000544570.5	TSL:5	c.1377G>A	p.Ala459Ala	synonymous	Exon 17 of 30	ENSP00000442256.1	O00408-3

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152186 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00186 AC: 464 AN: 250034 AF XY: 0.00176

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00234

Gnomad NFE exome AF: 0.00318

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00267 AC: 3901 AN: 1461068 Hom.: 14 Cov.: 34 AF XY: 0.00248 AC XY: 1800 AN XY: 726882

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00287 AC: 151 AN: 52624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00322 AC: 3579 AN: 1111996

Other (OTH) AF: 0.00152 AC: 92 AN: 60388

GnomAD4 genome AF: 0.00205 AC: 312 AN: 152304 Hom.: 2 Cov.: 33 AF XY: 0.00199 AC XY: 148 AN XY: 74472

African (AFR) AF: 0.000962 AC: 40 AN: 41566

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00348 AC: 237 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00292 Hom.: 1

Bravo AF: 0.00171

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00225

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		-2.0
PromoterAI		0.0070	Neutral
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs150054293; hg19: chr11-72295734; COSMIC: COSV57802376; COSMIC: COSV57802376;