2-182298082-T-G

Variant names:

• chr2-182298082-T-G
• rs833141
• NM_001363871.4:c.54-33668A>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.54-33668A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,232 control chromosomes in the GnomAD database, including 61,582 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 0.90 (61582 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.54-33668A>C		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.54-33668A>C		intron_variant	Intron 1 of 14	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136674 AN: 152114 Hom.: 61520 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.899 AC: 136795 AN: 152232 Hom.: 61582 Cov.: 32 AF XY: 0.899 AC XY: 66864 AN XY: 74414

African (AFR) AF: 0.942 AC: 39152 AN: 41560

American (AMR) AF: 0.932 AC: 14245 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4633 AN: 5170

South Asian (SAS) AF: 0.908 AC: 4376 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8897 AN: 10590

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59329 AN: 68012

Other (OTH) AF: 0.900 AC: 1898 AN: 2110

Alfa AF: 0.884 Hom.: 99092

Bravo AF: 0.907

Asia WGS AF: 0.892 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.50
DANN	Benign	0.75
PhyloP100		-0.082
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: rs833141; hg19: chr2-183162809;