Variant chr4-27002219-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020860.4(STIM2):c.628C>A(p.Pro210Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000139 in 1,442,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STIM2
NM_020860.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27922237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM2	NM_020860.4 linkuse as main transcript	c.628C>A	p.Pro210Thr	missense_variant, splice_region_variant	6/12	ENST00000467087.7	NP_065911.3	Q9P246-1B3KUB5
STIM2	NM_001169118.2 linkuse as main transcript	c.628C>A	p.Pro210Thr	missense_variant, splice_region_variant	6/13		NP_001162589.1	Q9P246H0Y860B3KUB5
STIM2	NM_001169117.2 linkuse as main transcript	c.628C>A	p.Pro210Thr	missense_variant, splice_region_variant	6/13		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.628C>A	p.Pro210Thr	missense_variant, splice_region_variant	6/12	1	NM_020860.4	ENSP00000419073.2		Q9P246-1A0A1X7SBY3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000852

AC:

AN:

234696

Hom.:

AF XY:

0.00000786

AC XY:

AN XY:

127152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1442750

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 11, 2024

The c.628C>A (p.P210T) alteration is located in exon 6 (coding exon 6) of the STIM2 gene. This alteration results from a C to A substitution at nucleotide position 628, causing the proline (P) at amino acid position 210 to be replaced by a threonine (T). 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

0.21

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.25

DEOGEN2

Benign

0.044

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

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;T;D;D;D;D;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.28

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

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.5

.;.;.;.;.;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.78

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

REVEL

Benign

0.26

Sift

Benign

0.59

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

Sift4G

Benign

0.18

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

Vest4

0.33, 0.34

MVP

0.64

ClinPred

0.53

GERP RS

5.2

Varity_R

0.31

gMVP

0.53

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