ClinVar Genomic variation as it relates to human health
NM_016648.4(LARP7):c.834dup (p.Arg279fs)
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_016648.4(LARP7):c.834dup (p.Arg279fs)
Variation ID: 504211 Accession: VCV000504211.19
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 4q25 4: 112647380-112647381 (GRCh38) [ NCBI UCSC ] 4: 113568536-113568537 (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 Apr 2, 2018 May 12, 2024 Apr 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_016648.4:c.834dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_057732.2:p.Arg279fs frameshift NM_001267039.1:c.855dupA NM_001267039.4:c.834dup NP_001253968.2:p.Arg279fs frameshift NM_001370974.1:c.834dup NP_001357903.1:p.Arg279fs frameshift NM_001370975.1:c.834dup NP_001357904.1:p.Arg279fs frameshift NM_001370976.1:c.831dup NP_001357905.1:p.Arg278fs frameshift NM_001370977.1:c.831dup NP_001357906.1:p.Arg278fs frameshift NM_001370978.1:c.834dup NP_001357907.1:p.Arg279fs frameshift NM_001370979.1:c.831dup NP_001357908.1:p.Arg278fs frameshift NM_001370980.1:c.831dup NP_001357909.1:p.Arg278fs frameshift NM_001370981.1:c.597dup NP_001357910.1:p.Arg200fs frameshift NM_001370982.1:c.597dup NP_001357911.1:p.Arg200fs frameshift NM_015454.3:c.834dup NP_056269.1:p.Arg279fs frameshift NM_016648.3:c.834dup NM_016648.3:c.834dupA NC_000004.12:g.112647386dup NC_000004.11:g.113568542dup NG_032779.1:g.15423dup - Protein change
- R279fs, R200fs, R278fs
- Other names
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- Canonical SPDI
- NC_000004.12:112647380:AAAAAA:AAAAAAA
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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
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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LARP7 | - | - |
GRCh38 GRCh37 |
116 | 287 | |
MIR302CHG | - | - | - | GRCh38 | - | 159 |
Conditions - Germline
Condition
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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
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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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Apr 29, 2023 | RCV000599079.12 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 27, 2022 | RCV001262130.6 |
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
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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
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Microcephalic primordial dwarfism, Alazami type
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001439893.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
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Pathogenic
(Oct 10, 2018)
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criteria provided, single submitter
Method: clinical testing
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Microcephalic primordial dwarfism, Alazami type
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367043.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
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Pathogenic
(Nov 08, 2022)
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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: SCV000710523.5
First in ClinVar: Apr 02, 2018 Last updated: Mar 04, 2023 |
Comment:
Observed with an intronic variant on the opposite allele (in trans) in a patient with short stature, developmental delay, abnormal muscle tone, thin corpus callosum, … (more)
Observed with an intronic variant on the opposite allele (in trans) in a patient with short stature, developmental delay, abnormal muscle tone, thin corpus callosum, and dysmorphic features (Wojcik et al., 2019); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31074943, 32888391) (less)
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Pathogenic
(Sep 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Microcephalic primordial dwarfism, Alazami type
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV002578131.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Observation 1:
Clinical Features:
Microcephaly (present) , Autism (present) , Anxiety (present) , Global developmental delay (present) , Short stature (present)
Sex: female
Tissue: Blood
Observation 2:
Clinical Features:
Microcephaly (present) , Autism (present) , Anxiety (present) , Global developmental delay (present) , Short stature (present)
Sex: female
Tissue: Blood
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Pathogenic
(Apr 29, 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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Invitae
Accession: SCV003300248.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 504211). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 504211). This premature translational stop signal has been observed in individual(s) with Alazami syndrome (PMID: 31074943). This variant is present in population databases (rs763929099, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Arg279Thrfs*5) in the LARP7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LARP7 are known to be pathogenic (PMID: 22865833, 26374271, 26607181). (less)
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Pathogenic
(Oct 01, 2022)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004148711.5
First in ClinVar: Nov 20, 2023 Last updated: May 12, 2024 |
Comment:
LARP7: PVS1, PM2
Number of individuals with the variant: 1
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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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Updating the neurodevelopmental profile of Alazami syndrome: Illustrating the role of developmental assessment in rare genetic disorders. | Wojcik MH | American journal of medical genetics. Part A | 2019 | PMID: 31074943 |
Broadening the phenotypic spectrum of pathogenic LARP7 variants: two cases with intellectual disability, variable growth retardation and distinct facial features. | Hollink IH | Journal of human genetics | 2016 | PMID: 26607181 |
Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability. | Ling TT | American journal of medical genetics. Part A | 2016 | PMID: 26374271 |
Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. | Alazami AM | Human mutation | 2012 | PMID: 22865833 |
Text-mined citations for rs763929099 ...
HelpRecord last updated May 12, 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.