Variant rs2230376 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002223.4(ITPR2):c.4482C>T(p.Pro1494Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,608,224 control chromosomes in the GnomAD database, including 76,962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5419 hom., cov: 32)

Exomes 𝑓: 0.31 ( 71543 hom. )

Consequence

ITPR2
NM_002223.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.82

Variant links:

Genes affected

ITPR2 (HGNC:6181): (inositol 1,4,5-trisphosphate receptor type 2) The protein encoded by this gene belongs to the inositol 1,4,5-triphosphate receptor family, whose members are second messenger intracellular calcium release channels. These proteins mediate a rise in cytoplasmic calcium in response to receptor activated production of inositol triphosphate. Inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. This protein is a type 2 receptor that consists of a cytoplasmic amino-terminus that binds inositol triphosphate, six membrane-spanning helices that contribute to the ion pore, and a short cytoplasmic carboxy-terminus. A mutation in this gene has been associated with anhidrosis, suggesting that intracellular calcium release mediated by this protein is required for eccrine sweat production. [provided by RefSeq, Apr 2015]

ITPR2 links:

ITPR2 (HGNC:):

ITPR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-3.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR2	NM_002223.4 linkuse as main transcript	c.4482C>T	p.Pro1494Pro	synonymous_variant	33/57	ENST00000381340.8	NP_002214.2	Q14571-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340.8 linkuse as main transcript	c.4482C>T	p.Pro1494Pro	synonymous_variant	33/57	1	NM_002223.4	ENSP00000370744.3		Q14571-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38288

AN:

151976

Hom.:

5417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.0830

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.269

AC:

66620

AN:

247824

Hom.:

9959

AF XY:

0.274

AC XY:

36868

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.0891

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.360

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.306

AC:

446290

AN:

1456130

Hom.:

71543

Cov.:

AF XY:

0.305

AC XY:

221174

AN XY:

724526

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.0783

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.252

AC:

38311

AN:

152094

Hom.:

5419

Cov.:

AF XY:

0.252

AC XY:

18712

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.0830

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.307

Hom.:

16069

Bravo

AF:

0.239

Asia WGS

AF:

0.207

AC:

721

AN:

3476

EpiCase

AF:

0.321

EpiControl

AF:

0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.14

DANN

Benign

0.32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over