rs2195611

Variant names:

• chr2-182391840-C-A
• rs2195611
• NM_001363871.4:c.53+34738G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-182391840-C-A
• chr2-182391840-C-T

Variant summary

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

The NM_001363871.4(PDE1A):​c.53+34738G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,020 control chromosomes in the GnomAD database, including 23,341 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 0.55 (23341 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.53+34738G>T		intron_variant	Intron 1 of 14	ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.53+34738G>T		intron_variant	Intron 1 of 14	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83200 AN: 151902 Hom.: 23313 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.548 AC: 83285 AN: 152020 Hom.: 23341 Cov.: 32 AF XY: 0.556 AC XY: 41296 AN XY: 74306

African (AFR) AF: 0.481 AC: 19940 AN: 41448

American (AMR) AF: 0.541 AC: 8266 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3470

East Asian (EAS) AF: 0.880 AC: 4543 AN: 5164

South Asian (SAS) AF: 0.711 AC: 3430 AN: 4824

European-Finnish (FIN) AF: 0.613 AC: 6469 AN: 10558

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 37001 AN: 67962

Other (OTH) AF: 0.571 AC: 1202 AN: 2106

Alfa AF: 0.538 Hom.: 39452

Bravo AF: 0.534

Asia WGS AF: 0.787 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.99
DANN	Benign	0.43
PhyloP100		-1.4
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: rs2195611; hg19: chr2-183256567;