2-182233510-A-G

Variant names:

• chr2-182233510-A-G
• rs1432518
• NM_001363871.4:c.417+922T>C

Variant summary

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

The NM_001363871.4(PDE1A):​c.417+922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,862 control chromosomes in the GnomAD database, including 33,088 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 0.66 (33088 hom., cov: 31)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363871.4. 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_001363871.4	MANE Select	c.417+922T>C		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.477+922T>C		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.465+922T>C		intron	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.417+922T>C		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.465+922T>C		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.465+922T>C		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100023 AN: 151744 Hom.: 33065 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.659 AC: 100085 AN: 151862 Hom.: 33088 Cov.: 31 AF XY: 0.657 AC XY: 48779 AN XY: 74192

African (AFR) AF: 0.642 AC: 26569 AN: 41398

American (AMR) AF: 0.679 AC: 10342 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2597 AN: 3466

East Asian (EAS) AF: 0.730 AC: 3769 AN: 5162

South Asian (SAS) AF: 0.756 AC: 3645 AN: 4820

European-Finnish (FIN) AF: 0.569 AC: 5978 AN: 10508

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45024 AN: 67948

Other (OTH) AF: 0.687 AC: 1452 AN: 2114

Alfa AF: 0.536 Hom.: 1549

Bravo AF: 0.665

Asia WGS AF: 0.763 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.85
PhyloP100		0.27
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: rs1432518; hg19: chr2-183098237;