5-71587428-GTGGGCCGTCCTGAGGTTAGCCCTGCGGCCGTGTGCCCGCGCCTCTCCCGCCGGGCCGCGCGCCTA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022132.5(MCCC2):c.5_69del(p.Trp2SerfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MCCC2
NM_022132.5 frameshift
NM_022132.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.93
Genes affected
MCCC2 (HGNC:6937): (methylcrotonyl-CoA carboxylase subunit 2) This gene encodes the small subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Mutations in this gene are associated with 3-Methylcrotonylglycinuria, an autosomal recessive disorder of leucine catabolism. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 143 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-71587428-GTGGGCCGTCCTGAGGTTAGCCCTGCGGCCGTGTGCCCGCGCCTCTCCCGCCGGGCCGCGCGCCTA-G is Pathogenic according to our data. Variant chr5-71587428-GTGGGCCGTCCTGAGGTTAGCCCTGCGGCCGTGTGCCCGCGCCTCTCCCGCCGGGCCGCGCGCCTA-G is described in ClinVar as [Pathogenic]. Clinvar id is 2871586.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCCC2 | NM_022132.5 | c.5_69del | p.Trp2SerfsTer35 | frameshift_variant | 1/17 | ENST00000340941.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCCC2 | ENST00000340941.11 | c.5_69del | p.Trp2SerfsTer35 | frameshift_variant | 1/17 | 1 | NM_022132.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-methylcrotonyl-CoA carboxylase 2 deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp2Serfs*35) in the MCCC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC2 are known to be pathogenic (PMID: 11181649, 22642865). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.