2-182174207-C-T

Variant names:

• chr2-182174207-C-T
• rs1991765
• NM_001363871.4:c.1516+11685G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000409365.6(PDE1A):​c.1516+11685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 151,920 control chromosomes in the GnomAD database, including 43,684 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 0.76 (43684 hom., cov: 32)
• Consequence: PDE1A ENST00000409365.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409365.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.1516+11685G>A		intron	N/A	NP_001350800.1
	PDE1A	NM_001258312.3		c.1576+11685G>A		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1564+11685G>A		intron	N/A	NP_001382187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1516+11685G>A		intron	N/A	ENSP00000386767.1
	PDE1A	ENST00000435564.6	TSL:1	c.1564+11685G>A		intron	N/A	ENSP00000410309.1
	PDE1A	ENST00000410103.2	TSL:1	c.1565-5917G>A		intron	N/A	ENSP00000387037.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114704 AN: 151802 Hom.: 43625 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.756 AC: 114824 AN: 151920 Hom.: 43684 Cov.: 32 AF XY: 0.760 AC XY: 56472 AN XY: 74268

African (AFR) AF: 0.809 AC: 33531 AN: 41456

American (AMR) AF: 0.768 AC: 11682 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1850 AN: 3466

East Asian (EAS) AF: 0.914 AC: 4711 AN: 5156

South Asian (SAS) AF: 0.735 AC: 3542 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8489 AN: 10586

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48482 AN: 67900

Other (OTH) AF: 0.735 AC: 1552 AN: 2112

Alfa AF: 0.714 Hom.: 19504

Bravo AF: 0.756

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.31
PhyloP100		-0.31
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: rs1991765; hg19: chr2-183038934;