2-182168293-GAAA-GAA

Variant names:

• chr2-182168293-GA-G
• rs78156757
• NM_001363871.4:c.1516+17598delT

Variant summary

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

The NM_001003683.3(PDE1A):​c.1565-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,237,142 control chromosomes in the GnomAD database, including 9,951 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3261 hom., cov: 25)
  • Exomes 𝑓: 0.22 (6690 hom.)
• Consequence: PDE1A NM_001003683.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659
• 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 2-182168293-GA-G is Benign according to our data. Variant chr2-182168293-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1268286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003683.3. 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.1516+17598delT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1576+17598delT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1564+17598delT		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.1516+17598delT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1564+17598delT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1565-4delT		splice_region intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 30533 AN: 135706 Hom.: 3249 Cov.: 25

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.353 AC: 40578 AN: 114962 AF XY: 0.349

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.416

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.221 AC: 243786 AN: 1101378 Hom.: 6690 Cov.: 0 AF XY: 0.222 AC XY: 121373 AN XY: 546820

African (AFR) AF: 0.253 AC: 6169 AN: 24374

American (AMR) AF: 0.350 AC: 9366 AN: 26722

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 3236 AN: 18596

East Asian (EAS) AF: 0.347 AC: 10717 AN: 30884

South Asian (SAS) AF: 0.248 AC: 15007 AN: 60418

European-Finnish (FIN) AF: 0.193 AC: 7348 AN: 37994

Middle Eastern (MID) AF: 0.170 AC: 719 AN: 4226

European-Non Finnish (NFE) AF: 0.212 AC: 181219 AN: 853094

Other (OTH) AF: 0.222 AC: 10005 AN: 45070

GnomAD4 genome AF: 0.225 AC: 30569 AN: 135764 Hom.: 3261 Cov.: 25 AF XY: 0.227 AC XY: 14855 AN XY: 65360

African (AFR) AF: 0.250 AC: 9293 AN: 37152

American (AMR) AF: 0.329 AC: 4543 AN: 13824

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 444 AN: 3208

East Asian (EAS) AF: 0.340 AC: 1644 AN: 4834

South Asian (SAS) AF: 0.249 AC: 1086 AN: 4366

European-Finnish (FIN) AF: 0.155 AC: 1137 AN: 7356

Middle Eastern (MID) AF: 0.137 AC: 36 AN: 262

European-Non Finnish (NFE) AF: 0.188 AC: 11697 AN: 62074

Other (OTH) AF: 0.251 AC: 463 AN: 1848

Alfa AF: 0.102 Hom.: 98

Bravo AF: 0.216

ClinVar

ClinVar submissions as Germline

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		0.66
Mutation Taster		=99/1	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: rs78156757; hg19: chr2-183033020; COSMIC: COSV59521882;