ClinVar Genomic variation as it relates to human health
NM_018136.5(ASPM):c.5510G>A (p.Gly1837Asp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(4); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_018136.5(ASPM):c.5510G>A (p.Gly1837Asp)
Variation ID: 157835 Accession: VCV000157835.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q31.3 1: 197103741 (GRCh38) [ NCBI UCSC ] 1: 197072871 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 23, 2014 Feb 14, 2024 Jul 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_018136.5:c.5510G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060606.3:p.Gly1837Asp missense NM_001206846.2:c.4066-7577G>A intron variant NC_000001.11:g.197103741C>T NC_000001.10:g.197072871C>T NG_015867.1:g.47954G>A - Protein change
- G1837D
- Other names
- -
- Canonical SPDI
- NC_000001.11:197103740:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00100 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00011
Trans-Omics for Precision Medicine (TOPMed) 0.00036
The Genome Aggregation Database (gnomAD), exomes 0.00051
Exome Aggregation Consortium (ExAC) 0.00054
1000 Genomes Project 30x 0.00078
1000 Genomes Project 0.00100
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ASPM | - | - |
GRCh38 GRCh37 |
1733 | 1781 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Mar 9, 2023 | RCV000145146.18 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000891999.16 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Mar 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly 5, primary, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003825125.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly 5, primary, autosomal recessive
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000192194.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Likely benign
(Aug 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000723468.2
First in ClinVar: Apr 09, 2018 Last updated: Sep 26, 2021 |
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Uncertain significance
(Jul 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly 5, primary, autosomal recessive
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768683.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. Disease-associated missense variants in this gene are rare but they have been reported (ClinVar, PMIDs: 20978018, 28004384). (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from glycine to aspartic acid (exon 18). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (136 heterozygotes, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (p.(Gly1837Arg), 1 heterozygote, 0 homozygotes). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (IQ9 domain among a series of repeated calmodulin-binding IQ domains; PDB, PMID: 29243349). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0808 - Previous reports of pathogenicity are conflicting. This variant has been reported as likely benign and VUS in ClinVar. It has also been reported as a heterozygous VUS in a patient with primary autosomal recessive microcephaly (PMID: 23611254) (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
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Likely benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001035852.4
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Microcephaly 5, primary, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001254669.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Autosomal recessive primary microcephaly due to ASPM mutations: An update. | Létard P | Human mutation | 2018 | PMID: 29243349 |
Genetic heterogeneity in Pakistani microcephaly families revisited. | Ahmad I | Clinical genetics | 2017 | PMID: 28004384 |
Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory. | Tan CA | Clinical genetics | 2014 | PMID: 23611254 |
A clinical and molecular genetic study of 112 Iranian families with primary microcephaly. | Darvish H | Journal of medical genetics | 2010 | PMID: 20978018 |
Text-mined citations for rs144969324 ...
HelpRecord last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.