chr2-182693960-T-C

Variant names:

• chr2-182693960-T-C
• rs415994
• XM_047444688.1:c.74+22731A>G

Variant summary

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

The XM_047444688.1(PDE1A):​c.74+22731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,086 control chromosomes in the GnomAD database, including 37,022 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 0.69 (37022 hom., cov: 32)
• Consequence: PDE1A XM_047444688.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 5 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]

LOC101929976 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	XM_047444688.1	c.74+22731A>G		intron_variant	Intron 1 of 15		XP_047300644.1
LOC101929976	XR_427200.3	n.451-7823A>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105477 AN: 151968 Hom.: 36976 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.694 AC: 105578 AN: 152086 Hom.: 37022 Cov.: 32 AF XY: 0.693 AC XY: 51522 AN XY: 74306

African (AFR) AF: 0.785 AC: 32582 AN: 41494

American (AMR) AF: 0.689 AC: 10529 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2752 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2718 AN: 5166

South Asian (SAS) AF: 0.711 AC: 3432 AN: 4826

European-Finnish (FIN) AF: 0.651 AC: 6869 AN: 10556

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

European-Non Finnish (NFE) AF: 0.654 AC: 44461 AN: 67978

Other (OTH) AF: 0.710 AC: 1499 AN: 2110

Alfa AF: 0.671 Hom.: 50476

Bravo AF: 0.694

Asia WGS AF: 0.634 AC: 2210 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	1.4
DANN	Benign	0.62
PhyloP100		-0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs415994; hg19: chr2-183558687;