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NM_000709.4(BCKDHA):c.854-2A>G AND Maple syrup urine disease

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Oct 28, 2023
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:
RCV001379040.8

Allele description [Variation Report for NM_000709.4(BCKDHA):c.854-2A>G]

NM_000709.4(BCKDHA):c.854-2A>G

Gene:
BCKDHA:branched chain keto acid dehydrogenase E1 subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000709.4(BCKDHA):c.854-2A>G
HGVS:
  • NC_000019.10:g.41422627A>G
  • NG_013004.1:g.29839A>G
  • NM_000709.4:c.854-2A>GMANE SELECT
  • NM_001164783.2:c.854-5A>G
  • NC_000019.9:g.41928532A>G
Links:
dbSNP: rs760494152
NCBI 1000 Genomes Browser:
rs760494152
Molecular consequence:
  • NM_001164783.2:c.854-5A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000709.4:c.854-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Maple syrup urine disease (MSUD)
Identifiers:
MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: PS248600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001576762Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Oct 28, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002033450Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 7, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Mutational spectrum of maple syrup urine disease in Spain.

Rodríguez-Pombo P, Navarrete R, Merinero B, Gómez-Puertas P, Ugarte M.

Hum Mutat. 2006 Jul;27(7):715.

PubMed [citation]
PMID:
16786533
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576762.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects an acceptor splice site in intron 6 of the BCKDHA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BCKDHA are known to be pathogenic (PMID: 16786533, 22593002). This variant is present in population databases (rs760494152, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with maple syrup urine disease (PMID: 31980395, 33300147; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 500713). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002033450.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024