11-72577555-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002599.5(PDE2A):c.2655C>T(p.Tyr885=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,607,156 control chromosomes in the GnomAD database, including 75,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (6624 hom., cov: 33)
  • Exomes 𝑓: 0.31 (68786 hom.)
• Consequence: PDE2A NM_002599.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0130

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-72577555-G-A is Benign according to our data. Variant chr11-72577555-G-A is described in ClinVar as [Benign]. Clinvar id is 1167963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.013 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE2A	NM_002599.5	c.2655C>T	p.Tyr885=	synonymous_variant	31/31	ENST00000334456.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE2A	ENST00000334456.10	c.2655C>T	p.Tyr885=	synonymous_variant	31/31	1	NM_002599.5	A1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44850 AN: 151942 Hom.: 6618 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.300 AC: 73795 AN: 245666 Hom.: 11283 AF XY: 0.305 AC XY: 40591 AN XY: 133204

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.349

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.306 AC: 444894 AN: 1455094 Hom.: 68786 Cov.: 36 AF XY: 0.308 AC XY: 222960 AN XY: 724118

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.295 AC: 44882 AN: 152062 Hom.: 6624 Cov.: 33 AF XY: 0.297 AC XY: 22106 AN XY: 74310

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.291

Alfa AF: 0.309 Hom.: 1612

Bravo AF: 0.290

Asia WGS AF: 0.291 AC: 1012 AN: 3476

EpiCase AF: 0.299

EpiControl AF: 0.300

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	3.2
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs1980091; hg19: chr11-72288599; COSMIC: COSV57804054; COSMIC: COSV57804054;