rs2623410

Positions:

• chr2-182307637-T-C
• chr2-182307637-T-G

Variant summary

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

The NM_001363871.4(PDE1A):​c.54-43223A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,150 control chromosomes in the GnomAD database, including 66,380 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 0.93 (66380 hom., cov: 31)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.54-43223A>G		intron_variant		ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.54-43223A>G		intron_variant		5	NM_001363871.4	ENSP00000386767	A1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141433 AN: 152032 Hom.: 66357 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.930 AC: 141509 AN: 152150 Hom.: 66380 Cov.: 31 AF XY: 0.931 AC XY: 69263 AN XY: 74410

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.937

Alfa AF: 0.956 Hom.: 8681

Bravo AF: 0.923

Asia WGS AF: 0.959 AC: 3335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.46

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: rs2623410; hg19: chr2-183172364;