2-182186694-A-G

Variant names:

• chr2-182186694-A-G
• rs7597711
• NM_001363871.4:c.1208-106T>C

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.1208-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,095,286 control chromosomes in the GnomAD database, including 294,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42627 hom., cov: 32)
  • Exomes 𝑓: 0.73 (252235 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0600
• Publications: 2 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=-0.73).
• BP6: Variant 2-182186694-A-G is Benign according to our data. Variant chr2-182186694-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 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.1208-106T>C		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1268-106T>C		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1256-106T>C		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.1208-106T>C		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1256-106T>C		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1256-106T>C		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113437 AN: 152002 Hom.: 42576 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.729 AC: 687135 AN: 943166 Hom.: 252235 AF XY: 0.726 AC XY: 346685 AN XY: 477804

African (AFR) AF: 0.781 AC: 16552 AN: 21192

American (AMR) AF: 0.791 AC: 19252 AN: 24328

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 9359 AN: 17814

East Asian (EAS) AF: 0.920 AC: 31994 AN: 34766

South Asian (SAS) AF: 0.699 AC: 40182 AN: 57474

European-Finnish (FIN) AF: 0.807 AC: 38662 AN: 47882

Middle Eastern (MID) AF: 0.624 AC: 1952 AN: 3130

European-Non Finnish (NFE) AF: 0.718 AC: 498968 AN: 694682

Other (OTH) AF: 0.721 AC: 30214 AN: 41898

GnomAD4 genome AF: 0.746 AC: 113545 AN: 152120 Hom.: 42627 Cov.: 32 AF XY: 0.750 AC XY: 55805 AN XY: 74368

African (AFR) AF: 0.780 AC: 32370 AN: 41512

American (AMR) AF: 0.762 AC: 11647 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3466

East Asian (EAS) AF: 0.913 AC: 4721 AN: 5170

South Asian (SAS) AF: 0.705 AC: 3403 AN: 4826

European-Finnish (FIN) AF: 0.802 AC: 8483 AN: 10582

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

European-Non Finnish (NFE) AF: 0.714 AC: 48561 AN: 67970

Other (OTH) AF: 0.728 AC: 1535 AN: 2108

Alfa AF: 0.676 Hom.: 2234

Bravo AF: 0.746

ClinVar

ClinVar submissions as Germline

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	-0.73
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		-0.060
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: rs7597711; hg19: chr2-183051421;