2-182168475-A-G

Variant names:

• chr2-182168475-A-G
• rs2276612
• NM_001363871.4:c.1516+17417T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1516+17417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,900 control chromosomes in the GnomAD database, including 6,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6275 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.209
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-182168475-A-G is Benign according to our data. Variant chr2-182168475-A-G is described in ClinVar as Benign. ClinVar VariationId is 1258905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 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.1516+17417T>C		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1576+17417T>C		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1564+17417T>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.1516+17417T>C		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1564+17417T>C		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1565-185T>C		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41544 AN: 151782 Hom.: 6271 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41544 AN: 151900 Hom.: 6275 Cov.: 32 AF XY: 0.278 AC XY: 20599 AN XY: 74212

African (AFR) AF: 0.145 AC: 6033 AN: 41466

American (AMR) AF: 0.283 AC: 4309 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1403 AN: 5160

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4814

European-Finnish (FIN) AF: 0.430 AC: 4532 AN: 10528

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.327 AC: 22235 AN: 67904

Other (OTH) AF: 0.261 AC: 549 AN: 2106

Alfa AF: 0.298 Hom.: 935

Bravo AF: 0.260

Asia WGS AF: 0.212 AC: 737 AN: 3472

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.21
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: rs2276612; hg19: chr2-183033202;