Genetic Variant ORAI2:c.*2096G>A (chr7-102449148-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001126340.3(ORAI2):c.*2096G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,026 control chromosomes in the GnomAD database, including 24,281 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 24272 hom., cov: 32)

Exomes 𝑓: 0.70 ( 9 hom. )

Consequence

ORAI2
NM_001126340.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ORAI2	NM_001126340.3 link	c.*2096G>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000495936.7	NP_001119812.1	Q96SN7
ORAI2	NM_001271818.2 link	c.*2096G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001258747.1	Q96SN7
ORAI2	NM_032831.4 link	c.*2096G>A	3_prime_UTR_variant	Exon 3 of 3		NP_116220.1	Q96SN7
ORAI2	NM_001271819.2 link	c.*2096G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001258748.1	B4DUB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI2	ENST00000495936.7 link	c.*2096G>A		3_prime_UTR_variant	Exon 4 of 4	2	NM_001126340.3	ENSP00000420178.2		Q96SN7C9JQR7

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83484

AN:

151876

Hom.:

24280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.700

AC:

AN:

Hom.:

Cov.:

AF XY:

0.773

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.549

AC:

83493

AN:

151996

Hom.:

24272

Cov.:

AF XY:

0.543

AC XY:

40349

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.359

AC:

14888

AN:

41474

American (AMR)

AF:

0.583

AC:

8889

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

2543

AN:

3472

East Asian (EAS)

AF:

0.390

AC:

2012

AN:

5164

South Asian (SAS)

AF:

0.501

AC:

2415

AN:

4820

European-Finnish (FIN)

AF:

0.577

AC:

6091

AN:

10558

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44719

AN:

67954

Other (OTH)

AF:

0.589

AC:

1242

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1816

3633

5449

7266

9082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.618

Hom.:

54829

Bravo

AF:

0.548

Asia WGS

AF:

0.429

AC:

1494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

(source)

DANN

Benign

0.54

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over