chr2-182201650-C-CA

Variant names:

• chr2-182201650-C-CA
• rs56413404
• NM_001363871.4:c.1004+37dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1004+37dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,253,636 control chromosomes in the GnomAD database, including 14,207 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8374 hom., cov: 0)
  • Exomes 𝑓: 0.25 (5833 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.543
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 2-182201650-C-CA is Benign according to our data. Variant chr2-182201650-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1233623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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+37dupT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+37dupT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+37dupT		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+37_1004+38insT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 45553 AN: 136608 Hom.: 8378 Cov.: 0

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.247 AC: 275699 AN: 1117030 Hom.: 5833 Cov.: 25 AF XY: 0.246 AC XY: 137252 AN XY: 556936

African (AFR) AF: 0.372 AC: 9152 AN: 24574

American (AMR) AF: 0.219 AC: 4458 AN: 20358

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 6658 AN: 18778

East Asian (EAS) AF: 0.0889 AC: 2925 AN: 32898

South Asian (SAS) AF: 0.241 AC: 14445 AN: 60028

European-Finnish (FIN) AF: 0.181 AC: 6435 AN: 35650

Middle Eastern (MID) AF: 0.325 AC: 1477 AN: 4544

European-Non Finnish (NFE) AF: 0.250 AC: 218078 AN: 872456

Other (OTH) AF: 0.253 AC: 12071 AN: 47744

GnomAD4 genome AF: 0.333 AC: 45544 AN: 136606 Hom.: 8374 Cov.: 0 AF XY: 0.331 AC XY: 21555 AN XY: 65032

African (AFR) AF: 0.474 AC: 17876 AN: 37736

American (AMR) AF: 0.280 AC: 3773 AN: 13482

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1550 AN: 3370

East Asian (EAS) AF: 0.0877 AC: 411 AN: 4684

South Asian (SAS) AF: 0.292 AC: 1239 AN: 4242

European-Finnish (FIN) AF: 0.229 AC: 1276 AN: 5584

Middle Eastern (MID) AF: 0.401 AC: 110 AN: 274

European-Non Finnish (NFE) AF: 0.288 AC: 18574 AN: 64478

Other (OTH) AF: 0.331 AC: 620 AN: 1874

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
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: rs56413404; hg19: chr2-183066377;