chr2-182354266-G-A

Position:

• chr2-182354266-G-A

Variant summary

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

The NM_001363871.4(PDE1A):​c.53+72312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,940 control chromosomes in the GnomAD database, including 6,096 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 0.27 (6096 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.53+72312C>T		intron_variant		ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.53+72312C>T		intron_variant		5	NM_001363871.4	ENSP00000386767	A1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41159 AN: 151822 Hom.: 6086 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.271 AC: 41195 AN: 151940 Hom.: 6096 Cov.: 32 AF XY: 0.275 AC XY: 20419 AN XY: 74250

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.271

Alfa AF: 0.296 Hom.: 3412

Bravo AF: 0.263

Asia WGS AF: 0.422 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.46
DANN	Benign	0.82

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: rs1438065; hg19: chr2-183218993;