2-182188931-C-G

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.1207+48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,260,056 control chromosomes in the GnomAD database, including 22,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2865 hom., cov: 33)
  • Exomes 𝑓: 0.18 (19643 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.366

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=-0.82).
• BP6: Variant 2-182188931-C-G is Benign according to our data. Variant chr2-182188931-C-G is described in ClinVar as [Benign]. Clinvar id is 1291679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1207+48G>C		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1207+48G>C		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28567 AN: 151970 Hom.: 2857 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.185 AC: 44145 AN: 238244 Hom.: 4593 AF XY: 0.187 AC XY: 24142 AN XY: 128870

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0864

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.318

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.183 AC: 203043 AN: 1107968 Hom.: 19643 Cov.: 14 AF XY: 0.183 AC XY: 103982 AN XY: 567136

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.0897

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.188 AC: 28600 AN: 152088 Hom.: 2865 Cov.: 33 AF XY: 0.191 AC XY: 14193 AN XY: 74350

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.173

Alfa AF: 0.119 Hom.: 265

Bravo AF: 0.181

Asia WGS AF: 0.249 AC: 867 AN: 3478

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	-0.82
Cadd	Benign	4.8
Dann	Benign	0.53

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: rs3769796; hg19: chr2-183053658;