rs288264

Positions:

• chr2-182714971-T-C
• chr2-182714971-T-G

Variant summary

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

The XM_047444688.1(PDE1A):​c.74+1720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,980 control chromosomes in the GnomAD database, including 32,660 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 0.65 (32660 hom., cov: 31)
• Consequence: PDE1A XM_047444688.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	XM_047444688.1	c.74+1720A>G		intron_variant			XP_047300644.1
		n.182714971T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99050 AN: 151862 Hom.: 32638 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99109 AN: 151980 Hom.: 32660 Cov.: 31 AF XY: 0.649 AC XY: 48247 AN XY: 74290

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.677

Alfa AF: 0.637 Hom.: 28383

Bravo AF: 0.644

Asia WGS AF: 0.603 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs288264; hg19: chr2-183579698;