rs7975290

Variant names:

• chr12-26460985-A-G
• rs7975290
• NM_002223.4:c.6342+14311T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-26460985-A-G
• chr12-26460985-A-T

Variant summary

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

The NM_002223.4(ITPR2):​c.6342+14311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 152,194 control chromosomes in the GnomAD database, including 243 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 0.050 (243 hom., cov: 32)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0994 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.6342+14311T>C		intron	N/A	NP_002214.2
	ITPR2	NM_001414174.1		c.6339+14311T>C		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.6124-17335T>C		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.6342+14311T>C		intron	N/A	ENSP00000370744.3
	ITPR2	ENST00000451599.6	TSL:1	n.*861+14311T>C		intron	N/A	ENSP00000408287.2

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7528 AN: 152076 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0667

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0495 AC: 7534 AN: 152194 Hom.: 243 Cov.: 32 AF XY: 0.0492 AC XY: 3658 AN XY: 74412

African (AFR) AF: 0.0394 AC: 1636 AN: 41500

American (AMR) AF: 0.0382 AC: 584 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3472

East Asian (EAS) AF: 0.0667 AC: 345 AN: 5174

South Asian (SAS) AF: 0.107 AC: 517 AN: 4830

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10598

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3686 AN: 68012

Other (OTH) AF: 0.0605 AC: 128 AN: 2114

Alfa AF: 0.0526 Hom.: 460

Bravo AF: 0.0493

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.50
PhyloP100		-0.35
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: rs7975290; hg19: chr12-26613918;