ClinVar Genomic variation as it relates to human health
NM_000430.4(PAFAH1B1):c.569-10T>C
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000430.4(PAFAH1B1):c.569-10T>C
Variation ID: 21182 Accession: VCV000021182.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.3 17: 2672645 (GRCh38) [ NCBI UCSC ] 17: 2575939 (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 May 3, 2013 Feb 14, 2024 Jun 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000430.4:c.569-10T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000017.11:g.2672645T>C NC_000017.10:g.2575939T>C NG_009799.1:g.84017T>C - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:2672644:T:C
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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PAFAH1B1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
521 | 604 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV000020304.14 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 25, 2017 | RCV000623782.3 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 7, 2023 | RCV000494023.16 | |
Likely pathogenic (1) |
no assertion criteria provided
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- | RCV001291184.2 |
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
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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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Pathogenic
(Jun 07, 2023)
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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: SCV000582158.7
First in ClinVar: Jul 02, 2017 Last updated: Jun 17, 2023 |
Comment:
Functional studies suggest c.569-10 T>C causes abnormal gene splicing (Philbert et al., 2017); In silico analysis supports a deleterious effect on splicing; Not observed at … (more)
Functional studies suggest c.569-10 T>C causes abnormal gene splicing (Philbert et al., 2017); In silico analysis supports a deleterious effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17664403, 11115846, 27891766, 29671837, 36100855) (less)
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Pathogenic
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000194389.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Dec 11, 2017)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000708127.2
First in ClinVar: Nov 23, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly due to LIS1 mutation
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001140211.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely pathogenic
(Jul 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000742598.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: African American
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Lissencephaly due to LIS1 mutation
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV004046079.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
This variant has been previously reported as a de novo change in patients with lissencephaly (PMID: 11115846, 27891766). Functional studies in patient fibroblasts demonstrated that … (more)
This variant has been previously reported as a de novo change in patients with lissencephaly (PMID: 11115846, 27891766). Functional studies in patient fibroblasts demonstrated that this variant leads to exon skipping (PMID: 27891766). It is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating the variant likely occurred as a de novo event. Based on the available evidence, the c.569-10T>C variant is classified as Pathogenic. (less)
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Pathogenic
(Aug 21, 2022)
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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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Invitae
Accession: SCV002160026.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in skipping of exon 7 and introduces a … (more)
For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in skipping of exon 7 and introduces a premature termination codon (PMID: 27891766). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 21182). This variant has been observed in individual(s) with lissencephaly (PMID: 11115846, 17664403, 27891766). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 6 of the PAFAH1B1 gene. It does not directly change the encoded amino acid sequence of the PAFAH1B1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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lissencephaly
Affected status: yes
Allele origin:
unknown
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479607.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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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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Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly. | Di Donato N | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29671837 |
A novel recurrent LIS1 splice site mutation in classic lissencephaly. | Philbert M | American journal of medical genetics. Part A | 2017 | PMID: 27891766 |
Location and type of mutation in the LIS1 gene do not predict phenotypic severity. | Uyanik G | Neurology | 2007 | PMID: 17664403 |
The location and type of mutation predict malformation severity in isolated lissencephaly caused by abnormalities within the LIS1 gene. | Cardoso C | Human molecular genetics | 2000 | PMID: 11115846 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAFAH1B1 | - | - | - | - |
Text-mined citations for rs113994202 ...
HelpRecord last updated Feb 14, 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.