rs3754929

Variant names:

• chr2-182223857-G-A
• rs3754929
• NM_001363871.4:c.776+7C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-182223857-G-A
• chr2-182223857-G-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.776+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,519,524 control chromosomes in the GnomAD database, including 343,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36109 hom., cov: 32)
  • Exomes 𝑓: 0.67 (307751 hom.)
• Consequence: PDE1A NM_001363871.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004992
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.179
• Publications: 13 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=-0.82).
• BP6: Variant 2-182223857-G-A is Benign according to our data. Variant chr2-182223857-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.776+7C>T		splice_region intron	N/A	NP_001350800.1
	PDE1A	NM_001258312.3		c.836+7C>T		splice_region intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.824+7C>T		splice_region intron	N/A	NP_001382187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.776+7C>T		splice_region intron	N/A	ENSP00000386767.1
	PDE1A	ENST00000435564.6	TSL:1	c.824+7C>T		splice_region intron	N/A	ENSP00000410309.1
	PDE1A	ENST00000410103.2	TSL:1	c.824+7C>T		splice_region intron	N/A	ENSP00000387037.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104351 AN: 151570 Hom.: 36077 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.707

GnomAD2 exomes AF: 0.673 AC: 144380 AN: 214446 AF XY: 0.679

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.713

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.670

GnomAD4 exome AF: 0.669 AC: 915298 AN: 1367836 Hom.: 307751 Cov.: 20 AF XY: 0.672 AC XY: 457744 AN XY: 681232

African (AFR) AF: 0.741 AC: 21893 AN: 29532

American (AMR) AF: 0.650 AC: 23246 AN: 35780

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 18476 AN: 24520

East Asian (EAS) AF: 0.706 AC: 25765 AN: 36480

South Asian (SAS) AF: 0.754 AC: 58095 AN: 77038

European-Finnish (FIN) AF: 0.575 AC: 30229 AN: 52546

Middle Eastern (MID) AF: 0.773 AC: 4302 AN: 5562

European-Non Finnish (NFE) AF: 0.662 AC: 694753 AN: 1049704

Other (OTH) AF: 0.680 AC: 38539 AN: 56674

GnomAD4 genome AF: 0.688 AC: 104428 AN: 151688 Hom.: 36109 Cov.: 32 AF XY: 0.686 AC XY: 50817 AN XY: 74122

African (AFR) AF: 0.740 AC: 30661 AN: 41432

American (AMR) AF: 0.691 AC: 10490 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2616 AN: 3458

East Asian (EAS) AF: 0.732 AC: 3762 AN: 5142

South Asian (SAS) AF: 0.757 AC: 3655 AN: 4830

European-Finnish (FIN) AF: 0.572 AC: 6032 AN: 10540

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45004 AN: 67780

Other (OTH) AF: 0.709 AC: 1498 AN: 2112

Alfa AF: 0.674 Hom.: 50242

Bravo AF: 0.697

Asia WGS AF: 0.763 AC: 2651 AN: 3476

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	-0.82
CADD	Benign	0.33
DANN	Benign	0.48
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000050
dbscSNV1_RF	Benign	0.0
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: rs3754929; hg19: chr2-183088584; COSMIC: COSV59530521; COSMIC: COSV59530521;