2-182494093-A-T

Variant names:

• chr2-182494093-A-T
• rs9332425
• ENST00000435564.6:c.101+28183T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435564.6(PDE1A):​c.101+28183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,118 control chromosomes in the GnomAD database, including 10,460 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 0.36 (10460 hom., cov: 32)
• Consequence: PDE1A ENST00000435564.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001258312.3	c.113+28183T>A		intron_variant	Intron 2 of 15		NP_001245241.1
PDE1A	NM_001395258.2	c.101+28183T>A		intron_variant	Intron 2 of 15		NP_001382187.1
PDE1A	NM_001395259.2	c.101+28183T>A		intron_variant	Intron 2 of 15		NP_001382188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000435564.6	c.101+28183T>A		intron_variant	Intron 1 of 14	1		ENSP00000410309.1
PDE1A	ENST00000410103.2	c.101+28183T>A		intron_variant	Intron 2 of 14	1		ENSP00000387037.1
PDE1A	ENST00000482782.6	c.101+28183T>A		intron_variant	Intron 2 of 15	4		ENSP00000512257.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54218 AN: 152000 Hom.: 10453 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.357 AC: 54237 AN: 152118 Hom.: 10460 Cov.: 32 AF XY: 0.362 AC XY: 26932 AN XY: 74360

African (AFR) AF: 0.225 AC: 9337 AN: 41516

American (AMR) AF: 0.467 AC: 7133 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3092 AN: 5174

South Asian (SAS) AF: 0.466 AC: 2240 AN: 4810

European-Finnish (FIN) AF: 0.401 AC: 4243 AN: 10582

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26244 AN: 67962

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.357 Hom.: 1244

Bravo AF: 0.356

Asia WGS AF: 0.493 AC: 1712 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	1.9
DANN	Benign	0.75
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9332425; hg19: chr2-183358820;