rs11048556

Variant names:

• chr12-26515735-G-A
• rs11048556
• NM_002223.4:c.5074-20475C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-26515735-G-A
• chr12-26515735-G-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.5074-20475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 151,820 control chromosomes in the GnomAD database, including 1,231 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 0.081 (1231 hom., cov: 30)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR2	NM_002223.4	c.5074-20475C>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.5074-20475C>T		intron_variant	Intron 37 of 56	1	NM_002223.4	ENSP00000370744.3

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12281 AN: 151702 Hom.: 1229 Cov.: 30

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0881

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

GnomAD4 genome AF: 0.0809 AC: 12289 AN: 151820 Hom.: 1231 Cov.: 30 AF XY: 0.0867 AC XY: 6431 AN XY: 74174

African (AFR) AF: 0.0313 AC: 1295 AN: 41430

American (AMR) AF: 0.224 AC: 3414 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2346 AN: 5108

South Asian (SAS) AF: 0.120 AC: 573 AN: 4794

European-Finnish (FIN) AF: 0.0895 AC: 942 AN: 10524

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0460 AC: 3125 AN: 67940

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.0708 Hom.: 802

Bravo AF: 0.0956

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.77
PhyloP100		-0.13
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: rs11048556; hg19: chr12-26668668;