rs761334309
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_016034.5(MRPS2):c.328C>T(p.Arg110Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,428 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 Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110H) has been classified as Likely benign.
Frequency
Consequence
NM_016034.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRPS2 | NM_016034.5 | c.328C>T | p.Arg110Cys | missense_variant | 4/4 | ENST00000241600.10 | |
LOC101928525 | NR_121579.1 | n.820G>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRPS2 | ENST00000241600.10 | c.328C>T | p.Arg110Cys | missense_variant | 4/4 | 1 | NM_016034.5 | P1 | |
ENST00000415062.1 | n.820G>A | non_coding_transcript_exon_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250148Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135358
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461316Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19AN XY: 726924
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation deficiency 36 Pathogenic:3
Pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Pathogenic, for Combined oxidative phosphorylation deficiency 36, autosomal recessive. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3-Very Strong => PS3 upgraded in strength to Very Strong (https://www.ncbi.nlm.nih.gov/pubmed/29576219). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 03, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Biochemistry, Assistance Publique Hopitaux de Paris - Bicetre Hospital | Nov 13, 2020 | The Arg110Cys variant in MRPS2 has been reported in 2 patients (one in heterozygous compound state and one in homozygous state). Mitochondrial respiratory chain complexes (I and IV) deficiencies were found in both patients. Typical clinical features of mitochondrial disorders (hyperlactatemia, hypoglycemia, hearing loss, neurological abnormaliites). The Arg110Cys variant fulfils the criteria to be classified as pathogenic on the basis of segregation studies, absence in controls and functional evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at