12-26538266-A-G

Position:

• chr12-26538266-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002223.4(ITPR2):​c.5073+11981T>C 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 151,982 control chromosomes in the GnomAD database, including 28,240 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 (28240 hom., cov: 31)
• Consequence: ITPR2 NM_002223.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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/exons	MANE	Protein	UniProt
ITPR2	NM_002223.4	c.5073+11981T>C		intron_variant		ENST00000381340.8	NP_002214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340.8	c.5073+11981T>C		intron_variant		1	NM_002223.4	ENSP00000370744	P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85920 AN: 151864 Hom.: 28239 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.565 AC: 85935 AN: 151982 Hom.: 28240 Cov.: 31 AF XY: 0.561 AC XY: 41684 AN XY: 74276

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.580

Alfa AF: 0.662 Hom.: 4404

Bravo AF: 0.530

Asia WGS AF: 0.425 AC: 1479 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs1531928; hg19: chr12-26691199;