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NM_022132.5(MCCC2):c.511+1G>A AND 3-methylcrotonyl-CoA carboxylase 2 deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 25, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002044282.5

Allele description [Variation Report for NM_022132.5(MCCC2):c.511+1G>A]

NM_022132.5(MCCC2):c.511+1G>A

Gene:
MCCC2:methylcrotonyl-CoA carboxylase subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q13.2
Genomic location:
Preferred name:
NM_022132.5(MCCC2):c.511+1G>A
HGVS:
  • NC_000005.10:g.71602634G>A
  • NG_008882.1:g.20347G>A
  • NM_001363147.1:c.511+1G>A
  • NM_022132.5:c.511+1G>AMANE SELECT
  • NC_000005.9:g.70898461G>A
Links:
dbSNP: rs1165990855
NCBI 1000 Genomes Browser:
rs1165990855
Molecular consequence:
  • NM_001363147.1:c.511+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_022132.5:c.511+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
3-methylcrotonyl-CoA carboxylase 2 deficiency
Synonyms:
METHYLCROTONYLGLYCINURIA, TYPE II; 3 alpha methylcrotonyl-CoA carboxylase 2 deficiency; 3 alpha methylcrotonylglycinuria 2; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008862; MedGen: C1859499; Orphanet: 6; OMIM: 210210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002112346Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 25, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.

Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, Baumgartner ER, Valle D.

J Clin Invest. 2001 Feb;107(4):495-504.

PubMed [citation]
PMID:
11181649
PMCID:
PMC199271
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002112346.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects a donor splice site in intron 5 of the MCCC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MCCC2 are known to be pathogenic (PMID: 11181649, 22642865). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MCCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1348372). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 25, 2025