NM_022132.5(MCCC2):c.100C>T (p.Gln34Ter) AND 3-methylcrotonyl-CoA carboxylase 2 deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003470071.4

Allele description [Variation Report for NM_022132.5(MCCC2):c.100C>T (p.Gln34Ter)]

NM_022132.5(MCCC2):c.100C>T (p.Gln34Ter)

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.100C>T (p.Gln34Ter)

HGVS:

NC_000005.10:g.71587525C>T
NG_008882.1:g.5238C>T
NG_105029.1:g.627C>T
NM_001363147.1:c.100C>T
NM_022132.5:c.100C>TMANE SELECT
NP_001350076.1:p.Gln34Ter
NP_071415.1:p.Gln34Ter
NC_000005.9:g.70883352C>T

Protein change:

Q34*

Links:

dbSNP: rs1413464990

Molecular consequence:

NM_001363147.1:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022132.5:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004194325	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 14, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005834471	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 4, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11181649, 22642865, 7601257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004194325

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 14, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005834471

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 4, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 (5)

Details of each submission

From Baylor Genetics, SCV004194325.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005834471.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln34*) 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). 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 premature translational stop signal has been observed in individual(s) with MCCC2-related conditions (PMID: 7601257). ClinVar contains an entry for this variant (Variation ID: 2676474). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 23, 2026

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