chr12-26336611-G-T

Position:

• chr12-26336611-G-T

Variant summary

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

The NM_002223.4(ITPR2):​c.*2786C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,022 control chromosomes in the GnomAD database, including 37,050 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 0.69 (37050 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ITPR2 NM_002223.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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]

ENSG00000255968 (HGNC:58268):

ENSG00000256185 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR2	NM_002223.4	c.*2786C>A		3_prime_UTR_variant	57/57	ENST00000381340.8	NP_002214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR2	ENST00000381340	c.*2786C>A		3_prime_UTR_variant	57/57	1	NM_002223.4	ENSP00000370744.3
ENSG00000255968	ENST00000535324.1	n.52+17607G>T		intron_variant		3
ENSG00000256185	ENST00000537724.1	n.126+214C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105440 AN: 151904 Hom.: 37001 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.728

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.694 AC: 105543 AN: 152022 Hom.: 37050 Cov.: 32 AF XY: 0.691 AC XY: 51362 AN XY: 74336

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.730

Alfa AF: 0.724 Hom.: 53203

Bravo AF: 0.688

Asia WGS AF: 0.697 AC: 2402 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.57

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: rs1049380; hg19: chr12-26489544;