2-182186236-C-G

Variant names:

• chr2-182186236-C-G
• rs1368216
• NM_001363871.4:c.1329-157G>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.1329-157G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,050 control chromosomes in the GnomAD database, including 3,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3410 hom., cov: 32)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-182186236-C-G is Benign according to our data. Variant chr2-182186236-C-G is described in ClinVar as Benign. ClinVar VariationId is 1267048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 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.1329-157G>C		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1389-157G>C		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1377-157G>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.1329-157G>C		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1377-157G>C		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1377-157G>C		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31087 AN: 151934 Hom.: 3397 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.205 AC: 31125 AN: 152050 Hom.: 3410 Cov.: 32 AF XY: 0.205 AC XY: 15202 AN XY: 74328

African (AFR) AF: 0.226 AC: 9385 AN: 41454

American (AMR) AF: 0.306 AC: 4674 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 442 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1696 AN: 5152

South Asian (SAS) AF: 0.229 AC: 1099 AN: 4808

European-Finnish (FIN) AF: 0.119 AC: 1258 AN: 10590

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11842 AN: 67992

Other (OTH) AF: 0.220 AC: 466 AN: 2114

Alfa AF: 0.0815 Hom.: 101

Bravo AF: 0.216

Asia WGS AF: 0.311 AC: 1080 AN: 3478

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	-0.83
CADD	Benign	4.3
DANN	Benign	0.45
PhyloP100		0.60
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: rs1368216; hg19: chr2-183050963;