rs3754929

chr2-182223857-G-Achr2-182223857-G-T

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.776+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,519,524 control chromosomes in the GnomAD database, including 343,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36109 hom., cov: 32)
  • Exomes 𝑓: 0.67 (307751 hom.)
• Consequence: PDE1A NM_001363871.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004992
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179

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 2-182223857-G-A is Benign according to our data. Variant chr2-182223857-G-A is described in ClinVar as [Benign]. Clinvar id is 1236025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.776+7C>T		splice_region_variant, intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.776+7C>T		splice_region_variant, intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104351 AN: 151570 Hom.: 36077 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.707

GnomAD3 exomes AF: 0.673 AC: 144380 AN: 214446 Hom.: 49071 AF XY: 0.679 AC XY: 79433 AN XY: 117016

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.713

Gnomad SAS exome AF: 0.756

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.670

GnomAD4 exome AF: 0.669 AC: 915298 AN: 1367836 Hom.: 307751 Cov.: 20 AF XY: 0.672 AC XY: 457744 AN XY: 681232

Gnomad4 AFR exome AF: 0.741

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.680

GnomAD4 genome AF: 0.688 AC: 104428 AN: 151688 Hom.: 36109 Cov.: 32 AF XY: 0.686 AC XY: 50817 AN XY: 74122

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.709

Alfa AF: 0.673 Hom.: 43038

Bravo AF: 0.697

Asia WGS AF: 0.763 AC: 2651 AN: 3476

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	0.33
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000050
dbscSNV1_RF	Benign	0.0
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: rs3754929; hg19: chr2-183088584; COSMIC: COSV59530521; COSMIC: COSV59530521;