rs11048674

Variant names:

• chr12-26759786-G-A
• rs11048674
• NM_002223.4:c.163+30371C>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.163+30371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,112 control chromosomes in the GnomAD database, including 552 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 0.036 (552 hom., cov: 32)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 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.163+30371C>T		intron	N/A	NP_002214.2	Q14571-1
	ITPR2	NM_001414174.1		c.163+30371C>T		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.163+30371C>T		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.163+30371C>T		intron	N/A	ENSP00000370744.3	Q14571-1
	ITPR2	ENST00000242737.5	TSL:1	c.163+30371C>T		intron	N/A	ENSP00000242737.5	Q14571-2
	ITPR2	ENST00000545235.1	TSL:1	n.93-34021C>T		intron	N/A	ENSP00000440548.1	F5GYT5

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5472 AN: 151994 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.00672

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0361 AC: 5488 AN: 152112 Hom.: 552 Cov.: 32 AF XY: 0.0419 AC XY: 3117 AN XY: 74348

African (AFR) AF: 0.00672 AC: 279 AN: 41502

American (AMR) AF: 0.186 AC: 2836 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1493 AN: 5180

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4822

European-Finnish (FIN) AF: 0.0437 AC: 462 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 67988

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0169 Hom.: 93

Bravo AF: 0.0502

Asia WGS AF: 0.135 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11048674; hg19: chr12-26912719;