rs149122641
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_014874.4(MFN2):c.1816G>A(p.Gly606Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,062 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 (★). Synonymous variant affecting the same amino acid position (i.e. G606G) has been classified as Likely benign.
Frequency
Consequence
NM_014874.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFN2 | NM_014874.4 | c.1816G>A | p.Gly606Ser | missense_variant | 16/19 | ENST00000235329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFN2 | ENST00000235329.10 | c.1816G>A | p.Gly606Ser | missense_variant | 16/19 | 1 | NM_014874.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251464Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727246
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 606 of the MFN2 protein (p.Gly606Ser). This variant is present in population databases (rs149122641, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 578960). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at