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NM_001352514.2(HLCS):c.1960+5G>A

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Aug 17, 2021)
Last evaluated:
Oct 20, 2020
Accession:
VCV000001912.7
Variation ID:
1912
Description:
single nucleotide variant
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NM_001352514.2(HLCS):c.1960+5G>A

Allele ID
16951
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
21q22.13
Genomic location
21: 36767213 (GRCh38) GRCh38 UCSC
21: 38139514 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000021.8:g.38139514C>T
NC_000021.9:g.36767213C>T
NM_001352514.2:c.1960+5G>A MANE Select
... more HGVS
Protein change
-
Other names
IVS10DS, G-A, +5
Canonical SPDI
NC_000021.9:36767212:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Links
ClinGen: CA278023
OMIM: 609018.0007
dbSNP: rs753887925
Varsome
Comment on variant
NCBI staff compared the intron-exon definition in AB063285.1 and the primers used to define the intron/exon boundaries in the paper by Yang et al., 2001 (PubMed 11735028) to define the location of this substitution.
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Oct 20, 2020 RCV000001989.9
Pathogenic 1 no assertion criteria provided Apr 7, 2020 RCV001566943.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
HLCS - - GRCh38
GRCh37
496 562

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Nov 08, 2017)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: unknown
Counsyl
Accession: SCV000795403.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (3)
Pathogenic
(Aug 10, 2018)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919518.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: HLCS c.1519+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
Pathogenic
(Oct 20, 2020)
criteria provided, single submitter
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Invitae
Accession: SCV000949761.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change falls in intron 8 of the HLCS gene. It does not directly change the encoded amino acid sequence of the HLCS protein. … (more)
Pathogenic
(Nov 01, 2001)
no assertion criteria provided
Method: literature only
HOLOCARBOXYLASE SYNTHETASE DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000022147.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Holocarboxylase synthetase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001456938.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Apr 07, 2020)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001790534.1
Submitted: (Aug 17, 2021)
Evidence details
Comment:
Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both in silico predictors and evolutionary conservation … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Holocarboxylase synthetase deficiency pre and post newborn screening. Donti TR Molecular genetics and metabolism reports 2016 PMID: 27114915
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. Yang X Human genetics 2001 PMID: 11735028
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. Sakamoto O European journal of pediatrics 2000 PMID: 10653324
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098

Text-mined citations for rs753887925...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 19, 2021