2-182186722-T-C

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.1208-134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 773,306 control chromosomes in the GnomAD database, including 14,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3425 hom., cov: 33)
  • Exomes 𝑓: 0.18 (11315 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.592

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=-0.84).
• BP6: Variant 2-182186722-T-C is Benign according to our data. Variant chr2-182186722-T-C is described in ClinVar as [Benign]. Clinvar id is 1253451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1208-134A>G		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1208-134A>G		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31147 AN: 152052 Hom.: 3411 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.181 AC: 112531 AN: 621136 Hom.: 11315 AF XY: 0.182 AC XY: 58385 AN XY: 321600

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.205 AC: 31187 AN: 152170 Hom.: 3425 Cov.: 33 AF XY: 0.205 AC XY: 15238 AN XY: 74404

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.219

Alfa AF: 0.184 Hom.: 322

Bravo AF: 0.216

Asia WGS AF: 0.306 AC: 1062 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 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.7
Dann	Benign	0.68

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: rs10930991; hg19: chr2-183051449;