rs149749759

Variant names:

• chr7-102439005-C-G
• rs149749759
• NM_001126340.3:c.49C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-102439005-C-G
• chr7-102439005-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001126340.3(ORAI2):​c.49C>G​(p.Pro17Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ORAI2 NM_001126340.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043375343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI2	NM_001126340.3	c.49C>G	p.Pro17Ala	missense_variant	Exon 3 of 4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2	c.49C>G	p.Pro17Ala	missense_variant	Exon 3 of 4		NP_001258747.1
ORAI2	NM_032831.4	c.49C>G	p.Pro17Ala	missense_variant	Exon 2 of 3		NP_116220.1
ORAI2	NM_001271819.2	c.-7+2672C>G		intron_variant	Intron 2 of 2		NP_001258748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI2	ENST00000495936.7	c.49C>G	p.Pro17Ala	missense_variant	Exon 3 of 4	2	NM_001126340.3	ENSP00000420178.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.33
DANN	Benign	0.64
DEOGEN2	Benign	0.052	T;T;T;T;T;T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T;.;T;T;.;T;.;T;.
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.043	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;N;.;N;.;N;.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.84	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.068
Sift	Benign	1.0	T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T;T;T;T;T
Polyphen		0.0010	.;B;B;.;B;.;B;.;B
Vest4		0.19, 0.20
MutPred		0.11		Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);
MVP		0.18
MPC		0.73
ClinPred		0.035	T
GERP RS		-3.4
Varity_R		0.018
gMVP		0.056

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

Other links and lift over

dbSNP: rs149749759; hg19: chr7-102079452;