NM_001352514.2(HLCS):c.2237-56_2255del AND Holocarboxylase synthetase deficiency

Clinical significance:Likely pathogenic (Last evaluated: Sep 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001376817.1

Allele description [Variation Report for NM_001352514.2(HLCS):c.2237-56_2255del]

NM_001352514.2(HLCS):c.2237-56_2255del

Gene:
HLCS:holocarboxylase synthetase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
21q22.13
Genomic location:
Preferred name:
NM_001352514.2(HLCS):c.2237-56_2255del
HGVS:
  • NC_000021.9:g.36756737_36756811del
  • NG_016193.2:g.238584_238658del
  • NM_000411.8:c.1796-56_1814del
  • NM_001242784.3:c.1796-56_1814del
  • NM_001242785.2:c.1796-56_1814del
  • NM_001352514.2:c.2237-56_2255delMANE SELECT
  • NM_001352515.2:c.1796-56_1814del
  • NM_001352516.2:c.1796-56_1814del
  • NM_001352517.1:c.1796-56_1814del
  • NM_001352518.2:c.1796-56_1814del
  • NC_000021.8:g.38129038_38129112del
  • NR_148020.2:n.2265_2339del
  • NR_148021.1:n.2422_2496del
Molecular consequence:
  • NR_148020.2:n.2265_2339del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.2422_2496del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000411.8:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001242784.3:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001242785.2:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001352514.2:c.2237-56_2255del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001352515.2:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001352516.2:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001352517.1:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001352518.2:c.1796-56_1814del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Holocarboxylase synthetase deficiency
Synonyms:
MULTIPLE CARBOXYLASE DEFICIENCY, EARLY ONSET
Identifiers:
MONDO: MONDO:0009666; MedGen: C0268581; Orphanet: 79242; OMIM: 253270

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001573989Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 7, 2019)
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

Citations

PubMed

Mutations in the holocarboxylase synthetase gene HLCS.

Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y.

Hum Mutat. 2005 Oct;26(4):285-90. Review.

PubMed [citation]
PMID:
16134170

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 Invitae, SCV001573989.1

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

Description

This variant results in the deletion of part of exon 11 (c.1796-56_1814del) of the HLCS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HLCS-related conditions. Loss-of-function variants in HLCS are known to be pathogenic (PMID: 16134170). 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: Oct 7, 2021

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