2-182142775-A-G

Position:

• chr2-182142775-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363871.4(PDE1A):​c.*307T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,060 control chromosomes in the GnomAD database, including 36,480 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 0.69 (36480 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.*307T>C		3_prime_UTR_variant	15/15	ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365	c.*307T>C		3_prime_UTR_variant	15/15	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104749 AN: 151942 Hom.: 36438 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.660

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.690 AC: 104849 AN: 152060 Hom.: 36480 Cov.: 32 AF XY: 0.695 AC XY: 51651 AN XY: 74344

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.664

Alfa AF: 0.661 Hom.: 31208

Bravo AF: 0.686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.67

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: rs1432531; hg19: chr2-183007502;