7-102439030-A-G

Position:

• chr7-102439030-A-G

Variant summary

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

The NM_001126340.3(ORAI2):​c.74A>G​(p.Asp25Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ORAI2 NM_001126340.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORAI2	NM_001126340.3	c.74A>G	p.Asp25Gly	missense_variant	3/4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2	c.74A>G	p.Asp25Gly	missense_variant	3/4		NP_001258747.1
ORAI2	NM_032831.4	c.74A>G	p.Asp25Gly	missense_variant	2/3		NP_116220.1
ORAI2	NM_001271819.2	c.-7+2697A>G		intron_variant			NP_001258748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORAI2	ENST00000495936.7	c.74A>G	p.Asp25Gly	missense_variant	3/4	2	NM_001126340.3	ENSP00000420178	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.74A>G (p.D25G) alteration is located in exon 3 (coding exon 1) of the ORAI2 gene. This alteration results from a A to G substitution at nucleotide position 74, causing the aspartic acid (D) at amino acid position 25 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;T;T;T;T;T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;.;D;D;.;D;.;D;.
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.8	.;L;L;.;L;.;L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-7.0	D;.;N;N;N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;.;T;T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;T;T;T;T;T;T;T;T
Polyphen		0.98	.;D;D;.;D;.;D;.;D
Vest4		0.84, 0.84
MutPred		0.15		Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);Gain of MoRF binding (P = 0.0475);
MVP		0.91
MPC		2.1
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102079477;