2-182201650-C-CAAAAA

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+38insTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,238,184 control chromosomes in the GnomAD database, including 4,135 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1790 hom., cov: 0)
  • Exomes 𝑓: 0.11 (2345 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-CAAAAA is Benign according to our data. Variant chr2-182201650-C-CAAAAA is described in ClinVar as [Benign]. Clinvar id is 1284004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.154 AC: 21023 AN: 136256 Hom.: 1789 Cov.: 0

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0772

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.112 AC: 123395 AN: 1101926 Hom.: 2345 Cov.: 25 AF XY: 0.110 AC XY: 60537 AN XY: 549286

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0614

Gnomad4 ASJ exome AF: 0.0609

Gnomad4 EAS exome AF: 0.0635

Gnomad4 SAS exome AF: 0.0610

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.154 AC: 21025 AN: 136258 Hom.: 1790 Cov.: 0 AF XY: 0.151 AC XY: 9776 AN XY: 64864

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0837

Gnomad4 EAS AF: 0.0853

Gnomad4 SAS AF: 0.0867

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.131

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 22, 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;