chr12-26338905-G-A

Position:

• chr12-26338905-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR2	NM_002223.4	c.*492C>T		3_prime_UTR_variant	57/57	ENST00000381340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR2	ENST00000381340.8	c.*492C>T		3_prime_UTR_variant	57/57	1	NM_002223.4	P1
	ENST00000535324.1	n.52+19901G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AMR exome AF: 0.409

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.850

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.786

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

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.623

Alfa AF: 0.617 Hom.: 28553

Bravo AF: 0.582

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.59

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: rs2570; hg19: chr12-26491838;