NM_001126340.3:c.625C>T

Variant names:

• chr7-102446912-C-T
• NM_001126340.3:c.625C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001126340.3(ORAI2):​c.625C>T​(p.Leu209Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ORAI2 NM_001126340.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3630867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI2	NM_001126340.3	c.625C>T	p.Leu209Phe	missense_variant	Exon 4 of 4	ENST00000495936.7	NP_001119812.1
ORAI2	NM_001271818.2	c.625C>T	p.Leu209Phe	missense_variant	Exon 4 of 4		NP_001258747.1
ORAI2	NM_032831.4	c.625C>T	p.Leu209Phe	missense_variant	Exon 3 of 3		NP_116220.1
ORAI2	NM_001271819.2	c.394C>T	p.Leu132Phe	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.625C>T	p.Leu209Phe	missense_variant	Exon 4 of 4	2	NM_001126340.3	ENSP00000420178.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;T;T;T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.91	.;D;D;.;D;.;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.66	N;N;.;N;.;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	.;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.023	.;D;D;D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D;D
Polyphen		0.75	P;P;.;P;.;P;P
Vest4		0.17
MutPred		0.68		Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);Loss of MoRF binding (P = 0.2459);
MVP		0.59
MPC		1.3
ClinPred		0.48	T
GERP RS		4.7
Varity_R		0.14
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102087359;