2-182201664-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001363871.4(PDE1A):c.1004+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 863,872 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (43 hom., cov: 27)
  • Exomes 𝑓: 0.048 (861 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 2-182201664-C-A is Benign according to our data. Variant chr2-182201664-C-A is described in ClinVar as [Benign]. Clinvar id is 1226653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1004+24G>T		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1004+24G>T		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 2958 AN: 90076 Hom.: 43 Cov.: 27

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.00850

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0721

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0378

GnomAD3 exomes AF: 0.102 AC: 9402 AN: 92446 Hom.: 177 AF XY: 0.105 AC XY: 5301 AN XY: 50314

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0254

Gnomad SAS exome AF: 0.117

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0795

GnomAD4 exome AF: 0.0481 AC: 37233 AN: 773796 Hom.: 861 Cov.: 22 AF XY: 0.0497 AC XY: 19484 AN XY: 392002

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.0984

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.0678

Gnomad4 FIN exome AF: 0.0640

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0329 AC: 2963 AN: 90076 Hom.: 43 Cov.: 27 AF XY: 0.0314 AC XY: 1358 AN XY: 43310

Gnomad4 AFR AF: 0.00774

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.00932

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0488

Gnomad4 OTH AF: 0.0378

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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.67
Dann	Benign	0.084

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200353420; hg19: chr2-183066391; COSMIC: COSV59519488;