chr7-76048180-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005918.4(MDH2):c.20G>C(p.Arg7Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000911 in 1,536,442 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005918.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDH2 | NM_005918.4 | c.20G>C | p.Arg7Pro | missense_variant | 1/9 | ENST00000315758.10 | |
MDH2 | NM_001282403.2 | c.20G>C | p.Arg7Pro | missense_variant | 1/8 | ||
MDH2 | NM_001282404.2 | c.-133G>C | 5_prime_UTR_variant | 1/8 | |||
MDH2 | NR_104165.2 | n.75G>C | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDH2 | ENST00000315758.10 | c.20G>C | p.Arg7Pro | missense_variant | 1/9 | 1 | NM_005918.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.00000702 AC: 1AN: 142396Hom.: 0 AF XY: 0.0000130 AC XY: 1AN XY: 76794
GnomAD4 exome AF: 0.00000867 AC: 12AN: 1384256Hom.: 0 Cov.: 52 AF XY: 0.0000117 AC XY: 8AN XY: 683364
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2023 | The p.R7P variant (also known as c.20G>C), located in coding exon 1 of the MDH2 gene, results from a G to C substitution at nucleotide position 20. The arginine at codon 7 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at