rs708156

Variant names:

• chr12-26539439-C-T
• rs708156
• NM_002223.4:c.5073+10808G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002223.4(ITPR2):​c.5073+10808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,996 control chromosomes in the GnomAD database, including 28,245 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 0.57 (28245 hom., cov: 31)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 5 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002223.4. 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
	ITPR2	NM_002223.4	MANE Select	c.5073+10808G>A		intron	N/A	NP_002214.2	Q14571-1
	ITPR2	NM_001414174.1		c.5070+10808G>A		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.5073+10808G>A		intron	N/A	NP_001401104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	ENST00000381340.8	TSL:1 MANE Select	c.5073+10808G>A		intron	N/A	ENSP00000370744.3	Q14571-1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85939 AN: 151880 Hom.: 28246 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.565 AC: 85949 AN: 151996 Hom.: 28245 Cov.: 31 AF XY: 0.561 AC XY: 41713 AN XY: 74292

African (AFR) AF: 0.256 AC: 10616 AN: 41450

American (AMR) AF: 0.476 AC: 7260 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1322 AN: 5164

South Asian (SAS) AF: 0.602 AC: 2899 AN: 4816

European-Finnish (FIN) AF: 0.737 AC: 7782 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51833 AN: 67960

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.647 Hom.: 4431

Bravo AF: 0.530

Asia WGS AF: 0.424 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.018
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: rs708156; hg19: chr12-26692372;