rs11048570

Variant names:

• chr12-26539754-G-A
• rs11048570
• NM_002223.4:c.5073+10493C>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.5073+10493C>T 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 152,106 control chromosomes in the GnomAD database, including 28,259 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 (28259 hom., cov: 32)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR2	NM_002223.4	c.5073+10493C>T		intron_variant	Intron 37 of 56	ENST00000381340.8	NP_002214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340.8	c.5073+10493C>T		intron_variant	Intron 37 of 56	1	NM_002223.4	ENSP00000370744.3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85991 AN: 151986 Hom.: 28258 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.565 AC: 86007 AN: 152106 Hom.: 28259 Cov.: 32 AF XY: 0.561 AC XY: 41734 AN XY: 74356

African (AFR) AF: 0.256 AC: 10626 AN: 41466

American (AMR) AF: 0.476 AC: 7283 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1323 AN: 5180

South Asian (SAS) AF: 0.601 AC: 2894 AN: 4818

European-Finnish (FIN) AF: 0.736 AC: 7783 AN: 10580

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

European-Non Finnish (NFE) AF: 0.763 AC: 51859 AN: 67992

Other (OTH) AF: 0.580 AC: 1225 AN: 2112

Alfa AF: 0.600 Hom.: 4553

Bravo AF: 0.530

Asia WGS AF: 0.424 AC: 1477 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.74
PhyloP100		-0.67
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: rs11048570; hg19: chr12-26692687;