NC_000002.11:g.(?_150426488)_(150426702_?)del AND Methylmalonic aciduria and homocystinuria type cblD

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 19, 2023
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:: RCV004582537.2

Allele description [Variation Report for NC_000002.11:g.(?_150426488)_(150426702_?)del]

NC_000002.11:g.(?_150426488)_(150426702_?)del

Gene:: MMADHC:metabolism of cobalamin associated D [Gene - OMIM - HGNC]
Variant type:: Deletion
Cytogenetic location:: 2q23.2
Genomic location:: Chr2: 150426488 - 150426702 (on Assembly GRCh37)
Preferred name:: NC_000002.11:g.(?_150426488)_(150426702_?)del
HGVS:: NC_000002.11:g.(?_150426488)_(150426702_?)del
This HGVS expression did not pass validation

Condition(s)

Name:: Methylmalonic aciduria and homocystinuria type cblD (MAHCD)
Synonyms:: METHYLMALONIC ACIDEMIA, cblH TYPE; Methylmalonic acidemia with homocystinuria cblD; Methylmalonic aciduria with homocystinuria cblD type
Identifiers:: MONDO: MONDO:0010185; MedGen: C1848552; Orphanet: 622; Orphanet: 79283; OMIM: 277410

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005067898	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 19, 2023)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18385497, 22156578, 25155779, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005067898

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 19, 2023)

unknown

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

Citations

PubMed

Gene identification for the cblD defect of vitamin B12 metabolism.

Coelho D, Suormala T, Stucki M, Lerner-Ellis JP, Rosenblatt DS, Newbold RF, Baumgartner MR, Fowler B.

N Engl J Med. 2008 Apr 3;358(14):1454-64. doi: 10.1056/NEJMoa072200.

PubMed [citation]

PMID:: 18385497

Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism.

Stucki M, Coelho D, Suormala T, Burda P, Fowler B, Baumgartner MR.

Hum Mol Genet. 2012 Mar 15;21(6):1410-8. doi: 10.1093/hmg/ddr579. Epub 2011 Dec 8.

PubMed [citation]

PMID:: 22156578

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005067898.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MMADHC protein in which other variant(s) (p.Tyr249Cys) have been determined to be pathogenic (PMID: 18385497, 22156578, 25155779). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is a gross deletion of the genomic region encompassing exon(s) 8 of the MMADHC gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with MMADHC-related conditions.

#	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

Last Updated: Sep 29, 2024

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