rs2570

Variant names:

• chr12-26338905-G-A
• rs2570
• NM_002223.4:c.*492C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-26338905-G-A
• chr12-26338905-G-C

Variant summary

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

The NM_002223.4(ITPR2):​c.*492C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,522 control chromosomes in the GnomAD database, including 26,993 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 0.59 (26910 hom., cov: 32)
  • Exomes 𝑓: 0.57 (83 hom.)
• Consequence: ITPR2 NM_002223.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 20 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)

ITPR2-AS2 (HGNC:58268):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 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.*492C>T		3_prime_UTR	Exon 57 of 57	NP_002214.2	Q14571-1
	ITPR2	NM_001414174.1		c.*492C>T		3_prime_UTR	Exon 57 of 57	NP_001401103.1
	ITPR2	NM_001414175.1		c.*492C>T		3_prime_UTR	Exon 55 of 55	NP_001401104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR2	ENST00000381340.8	TSL:1 MANE Select	c.*492C>T		3_prime_UTR	Exon 57 of 57	ENSP00000370744.3	Q14571-1
	ITPR2-AS2	ENST00000535324.1	TSL:3	n.52+19901G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89848 AN: 151944 Hom.: 26885 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.574 AC: 264 AN: 460 Hom.: 83 Cov.: 0 AF XY: 0.632 AC XY: 139 AN XY: 220

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.409 AC: 18 AN: 44

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.571 AC: 8 AN: 14

South Asian (SAS) AF: 0.850 AC: 17 AN: 20

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.565 AC: 201 AN: 356

Other (OTH) AF: 0.786 AC: 11 AN: 14

GnomAD4 genome AF: 0.591 AC: 89917 AN: 152062 Hom.: 26910 Cov.: 32 AF XY: 0.591 AC XY: 43931 AN XY: 74334

African (AFR) AF: 0.529 AC: 21961 AN: 41488

American (AMR) AF: 0.507 AC: 7747 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2407 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2485 AN: 5168

South Asian (SAS) AF: 0.725 AC: 3495 AN: 4818

European-Finnish (FIN) AF: 0.576 AC: 6081 AN: 10564

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43502 AN: 67964

Other (OTH) AF: 0.623 AC: 1313 AN: 2108

Alfa AF: 0.613 Hom.: 37116

Bravo AF: 0.582

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.59
PhyloP100		1.2
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: rs2570; hg19: chr12-26491838;