rs895964

Variant names:

• chr12-26705133-G-A
• rs895964
• NM_002223.4:c.951+6040C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-26705133-G-A
• chr12-26705133-G-C

Variant summary

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

The NM_002223.4(ITPR2):​c.951+6040C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,724 control chromosomes in the GnomAD database, including 11,628 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 0.37 (11628 hom., cov: 30)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	NM_002223.4	MANE Select	c.951+6040C>T		intron	N/A	NP_002214.2
	ITPR2	NM_001414174.1		c.951+6040C>T		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.951+6040C>T		intron	N/A	NP_001401104.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	ENST00000381340.8	TSL:1 MANE Select	c.951+6040C>T		intron	N/A	ENSP00000370744.3
	ITPR2	ENST00000540791.1	TSL:3	n.526+6040C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56001 AN: 151606 Hom.: 11626 Cov.: 30

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.369 AC: 56037 AN: 151724 Hom.: 11628 Cov.: 30 AF XY: 0.366 AC XY: 27115 AN XY: 74110

African (AFR) AF: 0.186 AC: 7699 AN: 41346

American (AMR) AF: 0.366 AC: 5584 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1484 AN: 5160

South Asian (SAS) AF: 0.344 AC: 1651 AN: 4794

European-Finnish (FIN) AF: 0.419 AC: 4393 AN: 10492

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32824 AN: 67890

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.445 Hom.: 26287

Bravo AF: 0.358

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		0.057
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: rs895964; hg19: chr12-26858066;