2-182168293-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000410103.2(PDE1A):c.1565-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,237,142 control chromosomes in the GnomAD database, including 9,951 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3261 hom., cov: 25)
  • Exomes 𝑓: 0.22 (6690 hom.)
• Consequence: PDE1A ENST00000410103.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659

Genes affected

PDE1A (HGNC:8774): (phosphodiesterase 1A) Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).[supplied by OMIM, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-182168293-GA-G is Benign according to our data. Variant chr2-182168293-GA-G is described in ClinVar as [Benign]. Clinvar id is 1268286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1516+17598del		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1516+17598del		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 30533 AN: 135706 Hom.: 3249 Cov.: 25

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.221 AC: 243786 AN: 1101378 Hom.: 6690 Cov.: 0 AF XY: 0.222 AC XY: 121373 AN XY: 546820

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.225 AC: 30569 AN: 135764 Hom.: 3261 Cov.: 25 AF XY: 0.227 AC XY: 14855 AN XY: 65360

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.251

Bravo AF: 0.216

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

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs78156757; hg19: chr2-183033020;