2-182201664-C-A

Variant names:

• chr2-182201664-C-A
• rs200353420
• NM_001363871.4:c.1004+24G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363871.4(PDE1A):​c.1004+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 863,872 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (43 hom., cov: 27)
  • Exomes 𝑓: 0.048 (861 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0430
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 2-182201664-C-A is Benign according to our data. Variant chr2-182201664-C-A is described in ClinVar as Benign. ClinVar VariationId is 1226653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0895 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.1004+24G>T		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+24G>T		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+24G>T		intron	N/A	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.1004+24G>T		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+24G>T		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+24G>T		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 2958 AN: 90076 Hom.: 43 Cov.: 27

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.00850

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0721

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0378

GnomAD2 exomes AF: 0.102 AC: 9402 AN: 92446 AF XY: 0.105

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0254

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0795

GnomAD4 exome AF: 0.0481 AC: 37233 AN: 773796 Hom.: 861 Cov.: 22 AF XY: 0.0497 AC XY: 19484 AN XY: 392002

African (AFR) AF: 0.0118 AC: 218 AN: 18546

American (AMR) AF: 0.0361 AC: 684 AN: 18926

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 1603 AN: 16286

East Asian (EAS) AF: 0.0133 AC: 372 AN: 27992

South Asian (SAS) AF: 0.0678 AC: 3225 AN: 47548

European-Finnish (FIN) AF: 0.0640 AC: 1973 AN: 30846

Middle Eastern (MID) AF: 0.0983 AC: 329 AN: 3348

European-Non Finnish (NFE) AF: 0.0475 AC: 27350 AN: 575374

Other (OTH) AF: 0.0423 AC: 1479 AN: 34930

GnomAD4 genome AF: 0.0329 AC: 2963 AN: 90076 Hom.: 43 Cov.: 27 AF XY: 0.0314 AC XY: 1358 AN XY: 43310

African (AFR) AF: 0.00774 AC: 212 AN: 27402

American (AMR) AF: 0.0243 AC: 226 AN: 9318

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 208 AN: 2350

East Asian (EAS) AF: 0.00932 AC: 23 AN: 2468

South Asian (SAS) AF: 0.0539 AC: 152 AN: 2820

European-Finnish (FIN) AF: 0.0335 AC: 139 AN: 4148

Middle Eastern (MID) AF: 0.0789 AC: 15 AN: 190

European-Non Finnish (NFE) AF: 0.0488 AC: 1934 AN: 39656

Other (OTH) AF: 0.0378 AC: 47 AN: 1244

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.084
PhyloP100		-0.043
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200353420; hg19: chr2-183066391; COSMIC: COSV59519488;