Variant 4-26995478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020860.4(STIM2):c.497C>T(p.Thr166Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000069 in 1,594,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

STIM2
NM_020860.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

STIM2 (HGNC:19205): (stromal interaction molecule 2) This gene is a member of the stromal interaction molecule (STIM) family and likely arose, along with related family member STIM1, from a common ancestral gene. The encoded protein functions to regulate calcium concentrations in the cytosol and endoplasmic reticulum, and is involved in the activation of plasma membrane Orai Ca(2+) entry channels. This gene initiates translation from a non-AUG (UUG) start site. A signal peptide is cleaved from the resulting protein. Multiple transcript variants result from alternative splicing. [provided by RefSeq, Dec 2009]

STIM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21975732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM2	NM_020860.4 linkuse as main transcript	c.497C>T	p.Thr166Met	missense_variant	4/12	ENST00000467087.7	NP_065911.3	Q9P246-1B3KUB5
STIM2	NM_001169118.2 linkuse as main transcript	c.497C>T	p.Thr166Met	missense_variant	4/13		NP_001162589.1	Q9P246H0Y860B3KUB5
STIM2	NM_001169117.2 linkuse as main transcript	c.497C>T	p.Thr166Met	missense_variant	4/13		NP_001162588.1	Q9P246-3B3KUB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM2	ENST00000467087.7 linkuse as main transcript	c.497C>T	p.Thr166Met	missense_variant	4/12	1	NM_020860.4	ENSP00000419073.2		Q9P246-1A0A1X7SBY3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

236322

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000585

Gnomad SAS exome

AF:

0.000143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000693

AC:

AN:

1442198

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717654

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 19, 2022

The c.497C>T (p.T166M) alteration is located in exon 4 (coding exon 4) of the STIM2 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the threonine (T) at amino acid position 166 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;.;.;T;T;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Benign

0.00047

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.22

T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.2

.;.;.;.;.;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

.;.;N;N;N;.;.

REVEL

Benign

0.14

Sift

Benign

0.067

.;.;T;T;T;.;.

Sift4G

Benign

0.065

T;T;T;T;T;.;.

Vest4

0.50, 0.49

MVP

0.58

ClinPred

0.49

GERP RS

4.6

Varity_R

0.30

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over