8-27515728-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001979.6(EPHX2):c.746G>A(p.Arg249His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R249C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001979.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHX2 | NM_001979.6 | c.746G>A | p.Arg249His | missense_variant | 7/19 | ENST00000521400.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHX2 | ENST00000521400.6 | c.746G>A | p.Arg249His | missense_variant | 7/19 | 1 | NM_001979.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251120Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135728
GnomAD4 exome AF: 0.000140 AC: 204AN: 1461608Hom.: 0 Cov.: 30 AF XY: 0.000150 AC XY: 109AN XY: 727118
GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74490
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2022 | The c.746G>A (p.R249H) alteration is located in exon 7 (coding exon 7) of the EPHX2 gene. This alteration results from a G to A substitution at nucleotide position 746, causing the arginine (R) at amino acid position 249 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