rs17649232

chr2-182140011-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462938.6(PDE1A):c.*4603A>G variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,320 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.054 (298 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: PDE1A ENST00000462938.6 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4			downstream_gene_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000462938.6	c.*4603A>G		3_prime_UTR_variant, NMD_transcript_variant	16/16	4
PDE1A	ENST00000409365.6			downstream_gene_variant		5	NM_001363871.4	A1
PDE1A	ENST00000435564.6			downstream_gene_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8175 AN: 152194 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0537 AC: 8173 AN: 152312 Hom.: 298 Cov.: 33 AF XY: 0.0534 AC XY: 3977 AN XY: 74468

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0557

Gnomad4 FIN AF: 0.0699

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0740 Hom.: 213

Bravo AF: 0.0491

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.2
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17649232; hg19: chr2-183004738;