NM_015702.3(MMADHC):c.764_765del (p.Ser255fs) AND Methylmalonic aciduria and homocystinuria type cblD

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 5, 2020
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:: RCV002016744.5

Allele description

NM_015702.3(MMADHC):c.764_765del (p.Ser255fs)

Gene:

MMADHC:metabolism of cobalamin associated D [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2q23.2

Genomic location:

Preferred name:

NM_015702.3(MMADHC):c.764_765del (p.Ser255fs)

HGVS:

NC_000002.12:g.149570101GA[1]
NG_009189.1:g.22714CT[1]
NM_015702.3:c.764_765delMANE SELECT
NP_056517.1:p.Ser255fs
NC_000002.11:g.150426614_150426615del
NC_000002.11:g.150426615GA[1]

Protein change:

S255fs

Links:

dbSNP: rs2105041468

NCBI 1000 Genomes Browser:

rs2105041468

Molecular consequence:

NM_015702.3:c.764_765del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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Mus musculus ring finger protein 123 (Rnf123), transcript variant 1, mRNA
Mus musculus ring finger protein 123 (Rnf123), transcript variant 1, mRNA
gi|2507987517|ref|NM_001311152.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002304027	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 5, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18385497, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002304027

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 5, 2020)

germline

clinical testing

PubMed (2)
[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	germline	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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002304027.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the protein in which other variant(s) (p.Leu259Pro) have been observed in individuals with MMADHC-related conditions (PMID: 18385497). This suggests that this may be a clinically significant region of the MMADHC protein. This variant has not been reported in the literature in individuals with MMADHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser255Cysfs*2) in the MMADHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the MMADHC protein.

#	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: Mar 5, 2024

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