2-182186236-C-G

Position:

• chr2-182186236-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1329-157G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,050 control chromosomes in the GnomAD database, including 3,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3410 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-182186236-C-G is Benign according to our data. Variant chr2-182186236-C-G is described in ClinVar as [Benign]. Clinvar id is 1267048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.1329-157G>C		intron_variant		ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.1329-157G>C		intron_variant		5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31087 AN: 151934 Hom.: 3397 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.205 AC: 31125 AN: 152050 Hom.: 3410 Cov.: 32 AF XY: 0.205 AC XY: 15202 AN XY: 74328

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.220

Alfa AF: 0.0815 Hom.: 101

Bravo AF: 0.216

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.45

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: rs1368216; hg19: chr2-183050963;