7-102446946-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001126340.3(ORAI2):c.659G>A(p.Arg220His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001126340.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ORAI2 | NM_001126340.3 | c.659G>A | p.Arg220His | missense_variant | Exon 4 of 4 | ENST00000495936.7 | NP_001119812.1 | |
ORAI2 | NM_001271818.2 | c.659G>A | p.Arg220His | missense_variant | Exon 4 of 4 | NP_001258747.1 | ||
ORAI2 | NM_032831.4 | c.659G>A | p.Arg220His | missense_variant | Exon 3 of 3 | NP_116220.1 | ||
ORAI2 | NM_001271819.2 | c.428G>A | p.Arg143His | missense_variant | Exon 3 of 3 | NP_001258748.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459642Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726210
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.659G>A (p.R220H) alteration is located in exon 4 (coding exon 2) of the ORAI2 gene. This alteration results from a G to A substitution at nucleotide position 659, causing the arginine (R) at amino acid position 220 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at