NM_002223.4:c.4630+3131T>C

Variant summary

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

The NM_002223.4(ITPR2):​c.4630+3131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,958 control chromosomes in the GnomAD database, including 3,271 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 0.20 ( 3271 hom., cov: 29)

Consequence

ITPR2
NM_002223.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.217

Publications

3 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

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=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITPR2NM_002223.4 linkc.4630+3131T>C intron_variant Intron 34 of 56 ENST00000381340.8 NP_002214.2 Q14571-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITPR2ENST00000381340.8 linkc.4630+3131T>C intron_variant Intron 34 of 56 1 NM_002223.4 ENSP00000370744.3 Q14571-1

Frequencies

GnomAD3 genomes
AF:
0.196
AC:
29760
AN:
151842
Hom.:
3259
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.272
Gnomad AMI
AF:
0.0932
Gnomad AMR
AF:
0.154
Gnomad ASJ
AF:
0.235
Gnomad EAS
AF:
0.0600
Gnomad SAS
AF:
0.307
Gnomad FIN
AF:
0.131
Gnomad MID
AF:
0.258
Gnomad NFE
AF:
0.170
Gnomad OTH
AF:
0.212
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.196
AC:
29807
AN:
151958
Hom.:
3271
Cov.:
29
AF XY:
0.193
AC XY:
14336
AN XY:
74272
show subpopulations
African (AFR)
AF:
0.273
AC:
11289
AN:
41386
American (AMR)
AF:
0.154
AC:
2348
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.235
AC:
815
AN:
3470
East Asian (EAS)
AF:
0.0598
AC:
309
AN:
5170
South Asian (SAS)
AF:
0.307
AC:
1479
AN:
4812
European-Finnish (FIN)
AF:
0.131
AC:
1389
AN:
10576
Middle Eastern (MID)
AF:
0.253
AC:
74
AN:
292
European-Non Finnish (NFE)
AF:
0.170
AC:
11572
AN:
67970
Other (OTH)
AF:
0.212
AC:
447
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1175
2350
3526
4701
5876
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
320
640
960
1280
1600
<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:
0.182
Hom.:
2600
Bravo
AF:
0.198
Asia WGS
AF:
0.180
AC:
627
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.0
DANN
Benign
0.29
PhyloP100
-0.22
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

Publications

Other links and lift over

dbSNP: rs16931011; hg19: chr12-26728515; COSMIC: COSV101190371; API