dbSNP rs11048476: ITPR2:c.7858-9051T>C (chr12-26349379-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002223.4(ITPR2):c.7858-9051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,086 control chromosomes in the GnomAD database, including 4,375 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 0.24 ( 4375 hom., cov: 32)

Consequence

ITPR2
NM_002223.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

isolated anhidrosis with normal sweat glands
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ITPR2 links:

ENSG00000255968 (HGNC:58268):

ENSG00000255968 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR2	NM_002223.4 link	c.7858-9051T>C		intron_variant	Intron 55 of 56	ENST00000381340.8	NP_002214.2	Q14571-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340.8 link	c.7858-9051T>C		intron_variant	Intron 55 of 56	1	NM_002223.4	ENSP00000370744.3		Q14571-1
ENSG00000255968	ENST00000535324.1 link	n.52+30375A>G		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35966

AN:

151968

Hom.:

4370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.250

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

GnomAD4 genome

AF:

0.237

AC:

35981

AN:

152086

Hom.:

4375

Cov.:

AF XY:

0.235

AC XY:

17448

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.237

AC:

9822

AN:

41454

American (AMR)

AF:

0.240

AC:

3671

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

962

AN:

3470

East Asian (EAS)

AF:

0.171

AC:

883

AN:

5176

South Asian (SAS)

AF:

0.236

AC:

1136

AN:

4822

European-Finnish (FIN)

AF:

0.181

AC:

1912

AN:

10572

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.246

AC:

16729

AN:

67986

Other (OTH)

AF:

0.249

AC:

526

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1413

2826

4239

5652

7065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.246

Hom.:

7515

Bravo

AF:

0.242

Asia WGS

AF:

0.185

AC:

644

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.87

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over