11-72577605-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_002599.5(PDE2A):c.2616-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,538,782 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: PDE2A NM_002599.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-72577605-AT-A is Benign according to our data. Variant chr11-72577605-AT-A is described in ClinVar as [Benign]. Clinvar id is 1599138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00243 (230/94460) while in subpopulation NFE AF= 0.00347 (182/52414). AF 95% confidence interval is 0.00306. There are 0 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE2A	NM_002599.5	c.2616-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000334456.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE2A	ENST00000334456.10	c.2616-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002599.5	A1

Frequencies

GnomAD3 genomes AF: 0.00244 AC: 230 AN: 94424 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000461

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00510

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.00216

GnomAD3 exomes AF: 0.00177 AC: 271 AN: 153236 Hom.: 0 AF XY: 0.00161 AC XY: 139 AN XY: 86208

Gnomad AFR exome AF: 0.000484

Gnomad AMR exome AF: 0.000598

Gnomad ASJ exome AF: 0.000278

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00510

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.000236

GnomAD4 exome AF: 0.00149 AC: 2156 AN: 1444322 Hom.: 6 Cov.: 29 AF XY: 0.00152 AC XY: 1092 AN XY: 719204

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00307

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.000932

GnomAD4 genome AF: 0.00243 AC: 230 AN: 94460 Hom.: 0 Cov.: 31 AF XY: 0.00244 AC XY: 111 AN XY: 45516

Gnomad4 AFR AF: 0.000423

Gnomad4 AMR AF: 0.000461

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00510

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.00214

Alfa AF: 0.000499 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000481 AC: 1 AN: 2088

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200122101; hg19: chr11-72288649;