7-102439157-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001126340.3(ORAI2):​c.201C>T​(p.Ser67Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,613,726 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 54 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 61 hom. )

Consequence

ORAI2
NM_001126340.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.44
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 7-102439157-C-T is Benign according to our data. Variant chr7-102439157-C-T is described in ClinVar as [Benign]. Clinvar id is 783502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.44 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ORAI2NM_001126340.3 linkc.201C>T p.Ser67Ser synonymous_variant Exon 3 of 4 ENST00000495936.7 NP_001119812.1 Q96SN7
ORAI2NM_001271818.2 linkc.201C>T p.Ser67Ser synonymous_variant Exon 3 of 4 NP_001258747.1 Q96SN7
ORAI2NM_032831.4 linkc.201C>T p.Ser67Ser synonymous_variant Exon 2 of 3 NP_116220.1 Q96SN7
ORAI2NM_001271819.2 linkc.-7+2824C>T intron_variant Intron 2 of 2 NP_001258748.1 B4DUB4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ORAI2ENST00000495936.7 linkc.201C>T p.Ser67Ser synonymous_variant Exon 3 of 4 2 NM_001126340.3 ENSP00000420178.2 Q96SN7C9JQR7

Frequencies

GnomAD3 genomes
AF:
0.0154
AC:
2340
AN:
152206
Hom.:
54
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0510
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00151
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000999
Gnomad OTH
AF:
0.0134
GnomAD3 exomes
AF:
0.00453
AC:
1131
AN:
249902
Hom.:
24
AF XY:
0.00336
AC XY:
455
AN XY:
135510
show subpopulations
Gnomad AFR exome
AF:
0.0515
Gnomad AMR exome
AF:
0.00362
Gnomad ASJ exome
AF:
0.000299
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.000787
Gnomad NFE exome
AF:
0.00111
Gnomad OTH exome
AF:
0.00393
GnomAD4 exome
AF:
0.00234
AC:
3426
AN:
1461402
Hom.:
61
Cov.:
31
AF XY:
0.00212
AC XY:
1540
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.0546
Gnomad4 AMR exome
AF:
0.00402
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.000566
Gnomad4 NFE exome
AF:
0.000916
Gnomad4 OTH exome
AF:
0.00474
GnomAD4 genome
AF:
0.0154
AC:
2345
AN:
152324
Hom.:
54
Cov.:
32
AF XY:
0.0148
AC XY:
1102
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0510
Gnomad4 AMR
AF:
0.00719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00151
Gnomad4 NFE
AF:
0.00100
Gnomad4 OTH
AF:
0.0132
Alfa
AF:
0.00790
Hom.:
12
Bravo
AF:
0.0177
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.00136
EpiControl
AF:
0.00172

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Aug 02, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.15
DANN
Benign
0.88

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.

Other links and lift over

dbSNP: rs1133472; hg19: chr7-102079604; COSMIC: COSV100709936; COSMIC: COSV100709936; API