2-182201650-C-CAA

Position:

• chr2-182201650-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1004+37_1004+38insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,244,806 control chromosomes in the GnomAD database, including 6,742 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3420 hom., cov: 0)
  • Exomes 𝑓: 0.20 (3322 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.543

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 -10 ACMG points.

• BP6: Variant 2-182201650-C-CAA is Benign according to our data. Variant chr2-182201650-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1231444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4	c.1004+37_1004+38insTT		intron_variant		ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6	c.1004+37_1004+38insTT		intron_variant		5	NM_001363871.4	A1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 28676 AN: 136604 Hom.: 3409 Cov.: 0

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.196 AC: 217165 AN: 1108204 Hom.: 3322 Cov.: 25 AF XY: 0.195 AC XY: 107707 AN XY: 552362

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.210 AC: 28689 AN: 136602 Hom.: 3420 Cov.: 0 AF XY: 0.212 AC XY: 13786 AN XY: 65042

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.223

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 15, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;