Variant 7-102439005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001126340.3(ORAI2):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ORAI2
NM_001126340.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.574

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007403046).

BP6

Variant 7-102439005-C-T is Benign according to our data. Variant chr7-102439005-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2347741.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ORAI2	NM_001126340.3 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	3/4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	3/4		NP_001258747.1
ORAI2	NM_032831.4 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	2/3		NP_116220.1
ORAI2	NM_001271819.2 linkuse as main transcript	c.-7+2672C>T		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.49C>T	p.Pro17Ser	missense_variant	3/4	2	NM_001126340.3	ENSP00000420178	P1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251140

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000486

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000582

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.26

DANN

Benign

0.65

DEOGEN2

Benign

0.032

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.69

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

M_CAP

Benign

0.0039

MetaRNN

Benign

0.0074

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

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

MutationTaster

Benign

0.88

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

1.3

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

REVEL

Benign

0.068

Sift

Benign

0.90

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.14, 0.14

MVP

0.14

MPC

0.76

ClinPred

0.0035

GERP RS

-3.4

Varity_R

0.018

gMVP

0.064

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