rs7963493

Variant names:

• chr12-26482142-C-T
• rs7963493
• NM_002223.4:c.6013-901G>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.6013-901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,984 control chromosomes in the GnomAD database, including 32,700 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 0.61 (32700 hom., cov: 31)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 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.6013-901G>A		intron	N/A	NP_002214.2	Q14571-1
	ITPR2	NM_001414174.1		c.6010-901G>A		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.6013-901G>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.6013-901G>A		intron	N/A	ENSP00000370744.3	Q14571-1
	ITPR2	ENST00000451599.6	TSL:1	n.*532-901G>A		intron	N/A	ENSP00000408287.2	H7C2X9

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91980 AN: 151866 Hom.: 32699 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.605 AC: 91997 AN: 151984 Hom.: 32700 Cov.: 31 AF XY: 0.606 AC XY: 45055 AN XY: 74304

African (AFR) AF: 0.216 AC: 8938 AN: 41440

American (AMR) AF: 0.668 AC: 10205 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2344 AN: 3464

East Asian (EAS) AF: 0.507 AC: 2619 AN: 5168

South Asian (SAS) AF: 0.674 AC: 3247 AN: 4818

European-Finnish (FIN) AF: 0.816 AC: 8615 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53853 AN: 67962

Other (OTH) AF: 0.612 AC: 1289 AN: 2106

Alfa AF: 0.721 Hom.: 46907

Bravo AF: 0.579

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		-0.20
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: rs7963493; hg19: chr12-26635075;