rs7955200

Variant names:

• chr12-26432896-C-T
• rs7955200
• NM_002223.4:c.6769+3325G>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.6769+3325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,940 control chromosomes in the GnomAD database, including 29,461 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 (29461 hom., cov: 31)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR2	NM_002223.4	c.6769+3325G>A		intron_variant	Intron 48 of 56	ENST00000381340.8	NP_002214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340.8	c.6769+3325G>A		intron_variant	Intron 48 of 56	1	NM_002223.4	ENSP00000370744.3
ITPR2	ENST00000451599.6	n.*1288+3325G>A		intron_variant	Intron 11 of 17	1		ENSP00000408287.2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92213 AN: 151822 Hom.: 29455 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.607 AC: 92250 AN: 151940 Hom.: 29461 Cov.: 31 AF XY: 0.602 AC XY: 44737 AN XY: 74264

African (AFR) AF: 0.433 AC: 17931 AN: 41440

American (AMR) AF: 0.547 AC: 8336 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1909 AN: 5158

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7602 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.728 AC: 49468 AN: 67950

Other (OTH) AF: 0.613 AC: 1293 AN: 2110

Alfa AF: 0.678 Hom.: 112181

Bravo AF: 0.588

Asia WGS AF: 0.446 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.96
DANN	Benign	0.66
PhyloP100		0.0050
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: rs7955200; hg19: chr12-26585829;