2-182142775-A-G

Variant names:

• chr2-182142775-A-G
• rs1432531
• NM_001363871.4:c.*307T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.*307T>C		3_prime_UTR	Exon 15 of 15	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.*307T>C		3_prime_UTR	Exon 16 of 16	NP_001245241.1
	PDE1A	NM_001395258.2		c.*307T>C		3_prime_UTR	Exon 16 of 16	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.*307T>C		3_prime_UTR	Exon 15 of 15	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.*307T>C		3_prime_UTR	Exon 15 of 15	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000961744.1		c.*307T>C		3_prime_UTR	Exon 16 of 16	ENSP00000631803.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.675 AC: 27994 AN: 41450

American (AMR) AF: 0.723 AC: 11051 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1732 AN: 3462

East Asian (EAS) AF: 0.890 AC: 4607 AN: 5174

South Asian (SAS) AF: 0.669 AC: 3225 AN: 4818

European-Finnish (FIN) AF: 0.771 AC: 8161 AN: 10580

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45775 AN: 67982

Other (OTH) AF: 0.664 AC: 1399 AN: 2108

Alfa AF: 0.668 Hom.: 46085

Bravo AF: 0.686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1432531; hg19: chr2-183007502;