NM_002223.4:c.7857+9824A>G

Variant names:

• chr12-26377610-T-C
• rs10771279
• NM_002223.4:c.7857+9824A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002223.4(ITPR2):​c.7857+9824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,012 control chromosomes in the GnomAD database, including 13,416 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 0.41 (13416 hom., cov: 31)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 8 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

ENSG00000255968 (HGNC:58268):

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 = 0.659 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	NM_002223.4	MANE Select	c.7857+9824A>G		intron	N/A	NP_002214.2
	ITPR2	NM_001414174.1		c.7854+9824A>G		intron	N/A	NP_001401103.1
	ITPR2	NM_001414175.1		c.7638+9824A>G		intron	N/A	NP_001401104.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	ENST00000381340.8	TSL:1 MANE Select	c.7857+9824A>G		intron	N/A	ENSP00000370744.3
	ENSG00000255968	ENST00000535324.1	TSL:3	n.53-23047T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61773 AN: 151894 Hom.: 13411 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.407 AC: 61799 AN: 152012 Hom.: 13416 Cov.: 31 AF XY: 0.414 AC XY: 30730 AN XY: 74312

African (AFR) AF: 0.288 AC: 11923 AN: 41456

American (AMR) AF: 0.553 AC: 8447 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3462

East Asian (EAS) AF: 0.678 AC: 3505 AN: 5168

South Asian (SAS) AF: 0.417 AC: 2010 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4775 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28236 AN: 67954

Other (OTH) AF: 0.405 AC: 855 AN: 2112

Alfa AF: 0.412 Hom.: 22354

Bravo AF: 0.414

Asia WGS AF: 0.473 AC: 1640 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.77
PhyloP100		-0.0040
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: rs10771279; hg19: chr12-26530543;