This sequence change creates a premature translational stop signal (p.Arg482Serfs*58) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_004260.4(RECQL4):c.1443dup (p.Arg482fs)
Germline
Classification
Help
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.
(1)
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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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004260.4(RECQL4):c.1443dup (p.Arg482fs)
Variation ID: 2020485 Accession: VCV002020485.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 8q24.3 8: 144515189-144515190 (GRCh38) [ NCBI UCSC ] 8: 145740573-145740574 (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 Feb 8, 2023 Feb 20, 2024 Jul 30, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004260.4:c.1443dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004251.4:p.Arg482fs frameshift NM_001413017.1:c.1345dup NP_001399946.1:p.Arg450Serfs frameshift NM_001413018.1:c.1441dup NP_001399947.1:p.Arg482Serfs frameshift NM_001413019.1:c.1441dup NP_001399948.1:p.Arg482Serfs frameshift NM_001413020.1:c.1345dup NP_001399949.1:p.Arg450Serfs frameshift NM_001413021.1:c.370dup NP_001399950.1:p.Arg125Serfs frameshift NM_001413022.1:c.370dup NP_001399951.1:p.Arg125Serfs frameshift NM_001413023.1:c.370dup NP_001399952.1:p.Arg125Serfs frameshift NM_001413024.1:c.370dup NP_001399953.1:p.Arg125Serfs frameshift NM_001413025.1:c.1312dup NP_001399954.1:p.Arg439Serfs frameshift NM_001413027.1:c.304dup NP_001399956.1:p.Arg103Serfs frameshift NM_001413028.1:c.370dup NP_001399957.1:p.Arg125Serfs frameshift NM_001413029.1:c.1090dup NP_001399958.1:p.Arg365Serfs frameshift NM_001413030.1:c.304dup NP_001399959.1:p.Arg103Serfs frameshift NM_001413031.1:c.304dup NP_001399960.1:p.Arg103Serfs frameshift NM_001413032.1:c.304dup NP_001399961.1:p.Arg103Serfs frameshift NM_001413033.1:c.1441dup NP_001399962.1:p.Arg482Serfs frameshift NM_001413034.1:c.370dup NP_001399963.1:p.Arg125Serfs frameshift NM_001413035.1:c.370dup NP_001399964.1:p.Arg125Serfs frameshift NM_001413036.1:c.1441dup NP_001399965.1:p.Arg482Serfs frameshift NM_001413037.1:c.370dup NP_001399966.1:p.Arg125Serfs frameshift NM_001413038.1:c.370dup NP_001399967.1:p.Arg125Serfs frameshift NM_001413039.1:c.1441dup NP_001399968.1:p.Arg482Serfs frameshift NM_001413040.1:c.370dup NP_001399969.1:p.Arg125Serfs frameshift NM_001413041.1:c.304dup NP_001399970.1:p.Arg103Serfs frameshift NM_001413042.1:c.370dup NP_001399971.1:p.Arg125Serfs frameshift NM_001413043.1:c.-27dup NR_182090.1:n.1490dup NR_182091.1:n.1490dup NR_182092.1:n.1490dup NC_000008.11:g.144515192dup NC_000008.10:g.145740576dup NG_016430.2:g.7637dup NG_033083.1:g.2228dup NG_033083.2:g.2202dup LRG_277:g.7637dup LRG_277t1:c.1443dup LRG_277p1:p.Arg482fs - Protein change
- R482fs
- Other names
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- Canonical SPDI
- NC_000008.11:144515189:AAA:AAAA
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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
Help
The frequency of the allele represented by this VCV record.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| RECQL4 | - | - |
GRCh38 GRCh37 |
4469 | 4838 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Jul 30, 2022 | RCV002857313.3 |
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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|---|---|---|---|---|---|
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Pathogenic
(Jul 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Baller-Gerold syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003224172.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg482Serfs*58) in the RECQL4 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg482Serfs*58) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
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. |
Comment:
This sequence change creates a premature translational stop signal (p.Arg482Serfs*58) in the RECQL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RECQL4 are known to be pathogenic (PMID: 12734318, 12952869). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. | Siitonen HA | Human molecular genetics | 2003 | PMID: 12952869 |
| Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. | Wang LL | Journal of the National Cancer Institute | 2003 | PMID: 12734318 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.