NM_022132.5(MCCC2):c.838G>T (p.Asp280Tyr) AND 3-methylcrotonyl-CoA carboxylase 2 deficiency

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Apr 9, 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:: RCV000002004.18

Allele description [Variation Report for NM_022132.5(MCCC2):c.838G>T (p.Asp280Tyr)]

NM_022132.5(MCCC2):c.838G>T (p.Asp280Tyr)

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.838G>T (p.Asp280Tyr)

HGVS:

NC_000005.10:g.71634977G>T
NG_008882.1:g.52690G>T
NM_001363147.1:c.724G>T
NM_022132.5:c.838G>TMANE SELECT
NP_001350076.1:p.Asp242Tyr
NP_071415.1:p.Asp280Tyr
NC_000005.9:g.70930804G>T
NM_022132.4:c.838G>T
Q9HCC0:p.Asp280Tyr

Protein change:

D242Y; ASP280TYR

Links:

UniProtKB: Q9HCC0#VAR_067199; OMIM: 609014.0009; dbSNP: rs119103226

NCBI 1000 Genomes Browser:

rs119103226

Molecular consequence:

NM_001363147.1:c.724G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022132.5:c.838G>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022162	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2007)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000955887	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 6, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17968484, 22030835, 22150417, 28018443, 28492532
SCV001622419	Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 13, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 17968484
SCV004194350	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 29, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005666607	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Uneventful clinical courses of Korean patients with methylcrotonylglycinuria and their common mutations.

Jung CW, Lee BH, Kim JH, Kim GH, Lee J, Choi JH, Yoo HW.

J Hum Genet. 2012 Jan;57(1):62-4. doi: 10.1038/jhg.2011.116. Epub 2011 Oct 27.

PubMed [citation]

PMID:: 22030835

Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA carboxylase deficiency.

Cho SY, Park HD, Lee YW, Ki CS, Lee SY, Sohn YB, Park SW, Kim SH, Ji S, Kim SJ, Choi EW, Kim CH, Ko AR, Paik KH, Lee DH, Jin DK.

Clin Genet. 2012 Jan;81(1):96-8. doi: 10.1111/j.1399-0004.2011.01704.x. No abstract available.

PubMed [citation]

PMID:: 22150417

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000022162.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the asp280-to-tyr (D280Y) mutation in the MCCC2 gene that was found in compound heterozygous state in a patient with MCC2 deficiency (MCC2D; 210210) by Uematsu et al. (2007), see 609014.0008.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000955887.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 280 of the MCCC2 protein (p.Asp280Tyr). This variant is present in population databases (rs119103226, gnomAD 0.09%). This missense change has been observed in individuals with 3 methylcrotonyl-CoA carboxylase deficiency (PMID: 17968484, 22030835, 22150417, 28018443). ClinVar contains an entry for this variant (Variation ID: 1927). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MCCC2 protein function with a positive predictive value of 80%. 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

From Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, SCV001622419.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

From Baylor Genetics, SCV004194350.2

#	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 Fulgent Genetics, Fulgent Genetics, SCV005666607.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

ClinVar

Relating variation to medicine