Variant 7-102439020-A-G 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_001126340.3(ORAI2):c.64A>G(p.Lys22Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,760 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ORAI2
NM_001126340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

ORAI2 (HGNC:21667): (ORAI calcium release-activated calcium modulator 2) Predicted to enable store-operated calcium channel activity. Predicted to be involved in store-operated calcium entry. Predicted to be located in growth cone. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ORAI2 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=0.11678916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ORAI2	NM_001126340.3 linkuse as main transcript	c.64A>G	p.Lys22Glu	missense_variant	3/4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2 linkuse as main transcript	c.64A>G	p.Lys22Glu	missense_variant	3/4		NP_001258747.1
ORAI2	NM_032831.4 linkuse as main transcript	c.64A>G	p.Lys22Glu	missense_variant	2/3		NP_116220.1
ORAI2	NM_001271819.2 linkuse as main transcript	c.-7+2687A>G		intron_variant			NP_001258748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORAI2	ENST00000495936.7 linkuse as main transcript	c.64A>G	p.Lys22Glu	missense_variant	3/4	2	NM_001126340.3	ENSP00000420178	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251150

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Oct 13, 2023

The c.64A>G (p.K22E) alteration is located in exon 3 (coding exon 1) of the ORAI2 gene. This alteration results from a A to G substitution at nucleotide position 64, causing the lysine (K) at amino acid position 22 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

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

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;.;T;T;.;T;.;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

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

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.0

D;.;N;N;N;N;N;N;N

REVEL

Benign

0.076

Sift

Pathogenic

0.0

D;.;T;T;T;T;T;T;T

Sift4G

Pathogenic

0.0

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

Polyphen

0.31

.;B;B;.;B;.;B;.;B

Vest4

0.33, 0.33

MutPred

0.26

Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);Loss of ubiquitination at K22 (P = 0.0034);

MVP

0.65

MPC

1.1

ClinPred

0.32

GERP RS

5.4

Varity_R

0.11

gMVP

0.39

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