7-102446841-C-G

Variant names:

• chr7-102446841-C-G
• rs766937231
• NM_001126340.3:c.554C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001126340.3(ORAI2):​c.554C>G​(p.Pro185Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,254 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ORAI2 NM_001126340.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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 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=0.12675568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI2	NM_001126340.3	c.554C>G	p.Pro185Arg	missense_variant	Exon 4 of 4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2	c.554C>G	p.Pro185Arg	missense_variant	Exon 4 of 4		NP_001258747.1
ORAI2	NM_032831.4	c.554C>G	p.Pro185Arg	missense_variant	Exon 3 of 3		NP_116220.1
ORAI2	NM_001271819.2	c.323C>G	p.Pro108Arg	missense_variant	Exon 3 of 3		NP_001258748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI2	ENST00000495936.7	c.554C>G	p.Pro185Arg	missense_variant	Exon 4 of 4	2	NM_001126340.3	ENSP00000420178.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250678 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135576

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74384

Gnomad4 AFR AF: 0.0000241

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: 0.00

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.58
DANN	Benign	0.95
DEOGEN2	Benign	0.22	T;T;T;T;T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.65	.;T;T;.;T;.;.
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.;L;.;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	.;N;N;N;N;N;N
REVEL	Benign	0.026
Sift	Uncertain	0.021	.;D;D;D;D;D;D
Sift4G	Benign	0.073	T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;.;B;B
Vest4		0.24
MutPred		0.35		Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);Loss of glycosylation at P185 (P = 0.0021);
MVP		0.30
MPC		0.80
ClinPred		0.021	T
GERP RS		0.65
Varity_R		0.034
gMVP		0.52

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: rs766937231; hg19: chr7-102087288;