rs199476115
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Mitomap GenBank:
Absent
Consequence
ND2
missense
missense
Scores
Apogee2
Pathogenic
Clinical Significance
LHON
Conservation
PhyloP100: 5.45
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
No frequency data in Mitomap. Probably very rare.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ND2 | unassigned_transcript_4794 use as main transcript | c.775G>A | p.Gly259Ser | missense_variant | 1/1 | |||
use as main transcript |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap
LHON
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Leber optic atrophy Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1992 | - - |
Mitochondrial disease Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Oct 09, 2023 | The m.5244G>A (p.G259S) variant in MT-ND2 has been reported in one family (PMID: 1634041) with Leber Hereditary Optic Neuropathy (LHON), however individuals in this family also harbored other mitochondrial DNA variants also associated with LHON, making the association of this variant to the primary mitochondrial disease features in these individuals unclear. Furthermore, to our knowledge, nuclear genetic testing was not performed. There are no reports of large families with this variant segregating with disease. There are no reported de novo occurrences of this variant to our knowledge. The computational predictor MitoTIP suggests this variant is pathogenic (77 percentile, PP3). This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on October 9, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PP3. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Apogee2
Pathogenic
Hmtvar
Pathogenic
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
DEOGEN2
Benign
T
LIST_S2
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A
PROVEAN
Pathogenic
D
Sift4G
Pathogenic
D
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at