2-182188917-T-A

Variant names:

• chr2-182188917-T-A
• rs10497595
• NM_001363871.4:c.1207+62A>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.1207+62A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,052,880 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (250 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (153 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.596
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-182188917-T-A is Benign according to our data. Variant chr2-182188917-T-A is described in ClinVar as Benign. ClinVar VariationId is 1289577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.1207+62A>T		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1267+62A>T		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1255+62A>T		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.1207+62A>T		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1255+62A>T		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1255+62A>T		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4857 AN: 152142 Hom.: 250 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.00379 AC: 3414 AN: 900618 Hom.: 153 AF XY: 0.00322 AC XY: 1516 AN XY: 470618

African (AFR) AF: 0.113 AC: 2512 AN: 22156

American (AMR) AF: 0.00655 AC: 264 AN: 40302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22152

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36550

South Asian (SAS) AF: 0.000209 AC: 15 AN: 71708

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52830

Middle Eastern (MID) AF: 0.00626 AC: 29 AN: 4636

European-Non Finnish (NFE) AF: 0.000413 AC: 251 AN: 608338

Other (OTH) AF: 0.00813 AC: 341 AN: 41946

GnomAD4 genome AF: 0.0319 AC: 4862 AN: 152262 Hom.: 250 Cov.: 33 AF XY: 0.0308 AC XY: 2290 AN XY: 74464

African (AFR) AF: 0.111 AC: 4606 AN: 41508

American (AMR) AF: 0.0112 AC: 172 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68032

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0256 Hom.: 22

Bravo AF: 0.0371

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.17
DANN	Benign	0.34
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: rs10497595; hg19: chr2-183053644;