NM_001918.5(DBT):c.1018-550A>G AND Maple syrup urine disease

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Sep 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000668558.3

Allele description [Variation Report for NM_001918.5(DBT):c.1018-550A>G]

NM_001918.5(DBT):c.1018-550A>G

Gene:
DBT:dihydrolipoamide branched chain transacylase E2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p21.2
Genomic location:
Preferred name:
NM_001918.5(DBT):c.1018-550A>G
Other names:
NM_001918.3:c.1017_1018ins[NC_000001.11:g.100207187_100207312]
HGVS:
  • NC_000001.11:g.100207186T>C
  • NG_011852.2:g.47668A>G
  • NM_001918.5:c.1018-550A>GMANE SELECT
  • NC_000001.10:g.100672742T>C
  • NM_001918.3:c.1018-550A>G
Note:
NCBI staff reviewed the sequence information reported in PubMed 9621512 Figs. 2 and 3 to determine the location of this allele on the current reference sequence.
Links:
OMIM: 248610.0005; dbSNP: rs796052135
NCBI 1000 Genomes Browser:
rs796052135
Molecular consequence:
  • NM_001918.5:c.1018-550A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Maple syrup urine disease (MSUD)
Synonyms:
Branched chain ketoaciduria; Branched-chain alpha-keto acid dehydrogenase deficiency; Keto acid decarboxylase deficiency
Identifiers:
MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: 248600; OMIM: PS248600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000793180Counsylcriteria provided, single submitter
Uncertain significance
(Jul 31, 2017)
unknownclinical testing

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

Citation Link,

SCV001400045Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 9, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain alpha-keto acid dehydrogenase complex.

Tsuruta M, Mitsubuchi H, Mardy S, Miura Y, Hayashida Y, Kinugasa A, Ishitsu T, Matsuda I, Indo Y.

J Hum Genet. 1998;43(2):91-100.

PubMed [citation]
PMID:
9621512

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Counsyl, SCV000793180.1

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

From Invitae, SCV001400045.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change falls in intron 8 of the DBT gene. It does not directly change the encoded amino acid sequence of the DBT protein. This variant has been observed to be homozygous in an individual affected with maple syrup urine disease (PMID: 9621512). ClinVar contains an entry for this variant (Variation ID: 11946). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 9621512). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: May 10, 2021

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