chr2-182201650-C-CAA

Variant names:

• chr2-182201650-C-CAA
• rs56413404
• NM_001363871.4:c.1004+36_1004+37dupTT

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+36_1004+37dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,244,806 control chromosomes in the GnomAD database, including 6,742 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3420 hom., cov: 0)
  • Exomes 𝑓: 0.20 (3322 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-CAA is Benign according to our data. Variant chr2-182201650-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1231444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 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+36_1004+37dupTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+36_1064+37dupTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+36_1052+37dupTT		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+38insTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 28676 AN: 136604 Hom.: 3409 Cov.: 0

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.196 AC: 217165 AN: 1108204 Hom.: 3322 Cov.: 25 AF XY: 0.195 AC XY: 107707 AN XY: 552362

African (AFR) AF: 0.270 AC: 6455 AN: 23938

American (AMR) AF: 0.279 AC: 5682 AN: 20394

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 3167 AN: 18280

East Asian (EAS) AF: 0.288 AC: 9491 AN: 32994

South Asian (SAS) AF: 0.216 AC: 12876 AN: 59716

European-Finnish (FIN) AF: 0.151 AC: 5322 AN: 35314

Middle Eastern (MID) AF: 0.180 AC: 806 AN: 4484

European-Non Finnish (NFE) AF: 0.189 AC: 164063 AN: 865838

Other (OTH) AF: 0.197 AC: 9303 AN: 47246

GnomAD4 genome AF: 0.210 AC: 28689 AN: 136602 Hom.: 3420 Cov.: 0 AF XY: 0.212 AC XY: 13786 AN XY: 65042

African (AFR) AF: 0.241 AC: 9071 AN: 37716

American (AMR) AF: 0.311 AC: 4193 AN: 13484

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 412 AN: 3360

East Asian (EAS) AF: 0.336 AC: 1572 AN: 4684

South Asian (SAS) AF: 0.247 AC: 1048 AN: 4240

European-Finnish (FIN) AF: 0.122 AC: 681 AN: 5592

Middle Eastern (MID) AF: 0.128 AC: 35 AN: 274

European-Non Finnish (NFE) AF: 0.171 AC: 11036 AN: 64488

Other (OTH) AF: 0.223 AC: 419 AN: 1882

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;