NM_172250.3(MMAA):c.184_185del (p.Lys62fs) AND Methylmalonic aciduria, cblA type

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 21, 2022
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:: RCV002914821.3

Allele description [Variation Report for NM_172250.3(MMAA):c.184_185del (p.Lys62fs)]

NM_172250.3(MMAA):c.184_185del (p.Lys62fs)

Gene:

MMAA:metabolism of cobalamin associated A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4q31.21

Genomic location:

Preferred name:

NM_172250.3(MMAA):c.184_185del (p.Lys62fs)

HGVS:

NC_000004.12:g.145639323_145639324del
NG_007536.2:g.45282_45283del
NM_001375644.1:c.184_185del
NM_172250.3:c.184_185delMANE SELECT
NP_001362573.1:p.Lys62fs
NP_758454.1:p.Lys62fs
LRG_1301t1:c.184_185del
LRG_1301:g.45282_45283del
LRG_1301p1:p.Lys62fs
NC_000004.11:g.146560474_146560475del
NC_000004.11:g.146560475_146560476del

Protein change:

K62fs

Molecular consequence:

NM_001375644.1:c.184_185del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172250.3:c.184_185del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Methylmalonic aciduria, cblA type (MACA)
Synonyms:: Methylmalonic aciduria, vitamin b12-responsive, due to defect in synthesis of adenosylcobalamin, cbla complementation type; MMA cbl A type; Methylmalonic acidemia cblA type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009613; MedGen: C1855109; Orphanet: 28; Orphanet: 79310; OMIM: 251100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003267080	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 21, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15523652, 15781192, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003267080

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 21, 2022)

germline

clinical testing

PubMed (3)
[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

Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism.

Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Doré C, Lepage P, Gravel RA, Rosenblatt DS.

Hum Mutat. 2004 Dec;24(6):509-16. Erratum in: Hum Mutat. 2005 Mar;25(3):317.

PubMed [citation]

PMID:: 15523652

Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.

Martínez MA, Rincón A, Desviat LR, Merinero B, Ugarte M, Pérez B.

Mol Genet Metab. 2005 Apr;84(4):317-25. Epub 2005 Jan 22.

PubMed [citation]

PMID:: 15781192

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003267080.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MMAA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys62Glufs*18) in the MMAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MMAA are known to be pathogenic (PMID: 15523652, 15781192).

#	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: Oct 8, 2024

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