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NM_020533.3(MCOLN1):c.406-2A>G

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 24, 2018
Accession:
VCV000005131.5
Variation ID:
5131
Description:
single nucleotide variant
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NM_020533.3(MCOLN1):c.406-2A>G

Allele ID
20170
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 7526759 (GRCh38) GRCh38 UCSC
19: 7591645 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.7526759A>G
NC_000019.9:g.7591645A>G
NM_020533.3:c.406-2A>G splice acceptor
NG_015806.1:g.9150A>G
Protein change
-
Other names
IVS3-2A>G
IVS3AS, A-G, -2
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00018
Trans-Omics for Precision Medicine (TOPMed) 0.00009
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00021
Links
ClinGen: CA284833
OMIM: 605248.0001
dbSNP: rs104886461
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 31, 2018 RCV000058927.3
Pathogenic 6 criteria provided, multiple submitters, no conflicts Dec 24, 2018 RCV000005438.7
Pathogenic 1 criteria provided, single submitter Nov 10, 2017 RCV000825567.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MCOLN1 - - GRCh38
GRCh37
109 127

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jan 20, 2016)
criteria provided, single submitter
Method: clinical testing
Mucolipidosis type IV
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000699455.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (1)
Pathogenic
(Dec 24, 2018)
criteria provided, single submitter
Method: clinical testing
Mucolipidosis type IV
Allele origin: germline
Invitae
Accession: SCV000755266.2
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change affects an acceptor splice site in intron 3 of the MCOLN1 gene. It is expected to disrupt RNA splicing and likely results ... (more)
Pathogenic
(Sep 24, 2018)
criteria provided, single submitter
Method: clinical testing
Mucolipidosis type IV
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915847.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (2)
Comment:
The MCOLN1 c.406-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. Across a ... (more)
Pathogenic
(Nov 10, 2017)
criteria provided, single submitter
Method: clinical testing
Mucolipidosis
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000966896.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The c.406-2A>G variant (NM_020433.2) in MCOLN1 has been reported in at least 12 homozygous and 1 compound heterozygous individuals with mucolipidosis type IV (B argal ... (more)
Pathogenic
(Nov 24, 2015)
criteria provided, single submitter
Method: clinical testing
Mucolipidosis type IV
Allele origin: unknown
Counsyl
Accession: SCV000485237.1
Submitted: (Nov 23, 2016)
Evidence details
Pathogenic
(Apr 08, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000230384.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/em...
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000577440.3
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.406-2 A>G splice site variant has been previously reported in individuals with mucolipidosistype IV (Bargal et al. 2000). The c.406-2 A>G variant has been ... (more)
Pathogenic
(Nov 01, 2000)
no assertion criteria provided
Method: literature only
MUCOLIPIDOSIS IV
Allele origin: germline
OMIM
Accession: SCV000025620.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Pathogenic
(Jul 30, 2015)
no assertion criteria provided
Method: literature only
Ganglioside sialidase deficiency
Allele origin: germline
GeneReviews
Accession: SCV000243819.1
Submitted: (Jul 30, 2015)
Evidence details
Other databases
http://www.ncbi.nlm.nih.gov/bo...
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: germline
SNPedia
Accession: SCV000090448.1
Submitted: (Apr 26, 2011)
Evidence details

Citations for this variant

Title Author Journal Year Link
Mucolipidosis IV Schiffmann R - 2015 PMID: 20301393
High-throughput carrier screening using TaqMan allelic discrimination. Fedick A PloS one 2013 PMID: 23555759
Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent. Kalman L The Journal of molecular diagnostics : JMD 2009 PMID: 19815695
Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population. Hantash FM The Journal of molecular diagnostics : JMD 2006 PMID: 16645217
Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population. Edelmann L American journal of human genetics 2002 PMID: 11845410
Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population. Bargal R Human mutation 2001 PMID: 11317355
Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Sun M Human molecular genetics 2000 PMID: 11030752
Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV. Bassi MT American journal of human genetics 2000 PMID: 11013137
Identification of the gene causing mucolipidosis type IV. Bargal R Nature genetics 2000 PMID: 10973263
Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes. Slaugenhaupt SA American journal of human genetics 1999 PMID: 10441585
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MCOLN1 - - - -
http://www.ncbi.nlm.nih.gov/books/NBK1214/ - - - -

Record last updated Oct 27, 2019