7-76048180-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005918.4(MDH2):c.20G>A(p.Arg7Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000358 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. R7P) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDH2 | NM_005918.4 | c.20G>A | p.Arg7Gln | missense_variant | 1/9 | ENST00000315758.10 | |
MDH2 | NM_001282403.2 | c.20G>A | p.Arg7Gln | missense_variant | 1/8 | ||
MDH2 | NM_001282404.2 | c.-133G>A | 5_prime_UTR_variant | 1/8 | |||
MDH2 | NR_104165.2 | n.75G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDH2 | ENST00000315758.10 | c.20G>A | p.Arg7Gln | missense_variant | 1/9 | 1 | NM_005918.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000140 AC: 2AN: 142396Hom.: 0 AF XY: 0.0000260 AC XY: 2AN XY: 76794
GnomAD4 exome AF: 0.0000383 AC: 53AN: 1384256Hom.: 0 Cov.: 52 AF XY: 0.0000351 AC XY: 24AN 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
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 7 of the MDH2 protein (p.Arg7Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MDH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1493339). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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