2-182201650-C-CAAAAAA

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+38insTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,104,006 control chromosomes in the GnomAD database, including 1,107 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (613 hom., cov: 0)
  • Exomes 𝑓: 0.077 (1107 hom.)
  • Failed GnomAD Quality Control
• 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-CAAAAAA is Benign according to our data. Variant chr2-182201650-C-CAAAAAA is described in ClinVar as [Benign]. Clinvar id is 1265372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11098 AN: 136364 Hom.: 613 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.0921

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0816

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0855

GnomAD4 exome AF: 0.0769 AC: 84878 AN: 1104006 Hom.: 1107 Cov.: 25 AF XY: 0.0770 AC XY: 42366 AN XY: 550066

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.0631

Gnomad4 ASJ exome AF: 0.0597

Gnomad4 EAS exome AF: 0.0601

Gnomad4 SAS exome AF: 0.0657

Gnomad4 FIN exome AF: 0.0738

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.0733

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0814 AC: 11097 AN: 136364 Hom.: 613 Cov.: 0 AF XY: 0.0799 AC XY: 5188 AN XY: 64894

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.0921

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0850

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 31, 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;