rs727504010
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_022132.5(MCCC2):c.994C>T(p.Arg332Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,586 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_022132.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCCC2 | NM_022132.5 | c.994C>T | p.Arg332Ter | stop_gained | 10/17 | ENST00000340941.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCCC2 | ENST00000340941.11 | c.994C>T | p.Arg332Ter | stop_gained | 10/17 | 1 | NM_022132.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251452Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135898
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461514Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727064
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74276
ClinVar
Submissions by phenotype
3-methylcrotonyl-CoA carboxylase 2 deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 26, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | May 13, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | This sequence change creates a premature translational stop signal (p.Arg332*) 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). This variant is present in population databases (rs727504010, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with 3MCC deficiency (PMID: 16010683). ClinVar contains an entry for this variant (Variation ID: 167279). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | Jan 24, 2023 | Dysmorphism: Short stature, triangular facies, blue sclera, hypospadias, ambiguous genitalia Clinical suspicion: Noonan syndrome/Atypical RS Genes of interest: DPH1/TMEM94 - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 20, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 21, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at