1-11980275-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The ENST00000444836(MFN2):c.-214C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 397,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000444836 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MFN2 | ENST00000675298 | c.-359C>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 19 | ENSP00000501839.1 | |||||
MFN2 | ENST00000675817 | c.-359C>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 20 | ENSP00000502422.1 | |||||
MFN2 | ENST00000444836 | c.-214C>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 18 | 2 | ENSP00000416338.1 |
Frequencies
GnomAD3 genomes AF: 0.000427 AC: 65AN: 152140Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.000322 AC: 79AN: 245696Hom.: 0 Cov.: 0 AF XY: 0.000337 AC XY: 42AN XY: 124564
GnomAD4 genome AF: 0.000427 AC: 65AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74442
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Hereditary motor and sensory neuropathy with optic atrophy Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at