2-182471741-T-C

Variant names:

• chr2-182471741-T-C
• rs10497603
• ENST00000435564.6:c.101+50535A>G

Variant summary

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

The NM_001258312.3(PDE1A):​c.113+50535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,706 control chromosomes in the GnomAD database, including 2,481 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 0.16 (2481 hom., cov: 32)
• Consequence: PDE1A NM_001258312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001258312.3		c.113+50535A>G		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.101+50535A>G		intron	N/A	NP_001382187.1	P54750-4
	PDE1A	NM_001395259.2		c.101+50535A>G		intron	N/A	NP_001382188.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000435564.6	TSL:1	c.101+50535A>G		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.101+50535A>G		intron	N/A	ENSP00000387037.1	P54750-1
	PDE1A	ENST00000482782.6	TSL:4	c.101+50535A>G		intron	N/A	ENSP00000512257.1	P54750-4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24644 AN: 151588 Hom.: 2480 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.162 AC: 24643 AN: 151706 Hom.: 2481 Cov.: 32 AF XY: 0.172 AC XY: 12730 AN XY: 74132

African (AFR) AF: 0.0529 AC: 2194 AN: 41488

American (AMR) AF: 0.266 AC: 4033 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1026 AN: 5126

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2708 AN: 10574

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11893 AN: 67746

Other (OTH) AF: 0.180 AC: 377 AN: 2100

Alfa AF: 0.179 Hom.: 1467

Bravo AF: 0.157

Asia WGS AF: 0.181 AC: 625 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.32
PhyloP100		0.12
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: rs10497603; hg19: chr2-183336468;