2-182186694-A-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.1208-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,095,286 control chromosomes in the GnomAD database, including 294,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42627 hom., cov: 32)
  • Exomes 𝑓: 0.73 (252235 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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=-0.73).
• BP6: Variant 2-182186694-A-G is Benign according to our data. Variant chr2-182186694-A-G is described in ClinVar as [Benign]. Clinvar id is 1239898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1208-106T>C		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1208-106T>C		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113437 AN: 152002 Hom.: 42576 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.729 AC: 687135 AN: 943166 Hom.: 252235 AF XY: 0.726 AC XY: 346685 AN XY: 477804

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.699

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.746 AC: 113545 AN: 152120 Hom.: 42627 Cov.: 32 AF XY: 0.750 AC XY: 55805 AN XY: 74368

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.728

Alfa AF: 0.666 Hom.: 1988

Bravo AF: 0.746

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.9
Dann	Benign	0.86

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: rs7597711; hg19: chr2-183051421;