For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His478Thrfs*80) 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).
ClinVar Genomic variation as it relates to human health
NM_004260.4(RECQL4):c.1431del (p.His478fs)
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)
Help
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.1431del (p.His478fs)
Variation ID: 2029920 Accession: VCV002029920.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 8q24.3 8: 144515202 (GRCh38) [ NCBI UCSC ] 8: 145740586 (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 Jan 4, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004260.4:c.1431del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004251.4:p.His478fs frameshift NM_001413017.1:c.1332delG NP_001399946.1:p.His446Thrfs frameshift NM_001413018.1:c.1428delG NP_001399947.1:p.His478Thrfs frameshift NM_001413019.1:c.1428delG NP_001399948.1:p.His478Thrfs frameshift NM_001413020.1:c.1332delG NP_001399949.1:p.His446Thrfs frameshift NM_001413021.1:c.357delG NP_001399950.1:p.His121Thrfs frameshift NM_001413022.1:c.357delG NP_001399951.1:p.His121Thrfs frameshift NM_001413023.1:c.357delG NP_001399952.1:p.His121Thrfs frameshift NM_001413024.1:c.357delG NP_001399953.1:p.His121Thrfs frameshift NM_001413025.1:c.1299delG NP_001399954.1:p.His435Thrfs frameshift NM_001413027.1:c.291delG NP_001399956.1:p.His99Thrfs frameshift NM_001413028.1:c.357delG NP_001399957.1:p.His121Thrfs frameshift NM_001413029.1:c.1077delG NP_001399958.1:p.His361Thrfs frameshift NM_001413030.1:c.291delG NP_001399959.1:p.His99Thrfs frameshift NM_001413031.1:c.291delG NP_001399960.1:p.His99Thrfs frameshift NM_001413032.1:c.291delG NP_001399961.1:p.His99Thrfs frameshift NM_001413033.1:c.1428delG NP_001399962.1:p.His478Thrfs frameshift NM_001413034.1:c.357delG NP_001399963.1:p.His121Thrfs frameshift NM_001413035.1:c.357delG NP_001399964.1:p.His121Thrfs frameshift NM_001413036.1:c.1428delG NP_001399965.1:p.His478Thrfs frameshift NM_001413037.1:c.357delG NP_001399966.1:p.His121Thrfs frameshift NM_001413038.1:c.357delG NP_001399967.1:p.His121Thrfs frameshift NM_001413039.1:c.1428delG NP_001399968.1:p.His478Thrfs frameshift NM_001413040.1:c.357delG NP_001399969.1:p.His121Thrfs frameshift NM_001413041.1:c.291delG NP_001399970.1:p.His99Thrfs frameshift NM_001413042.1:c.357delG NP_001399971.1:p.His121Thrfs frameshift NM_001413043.1:c.-40delG NR_182090.1:n.1477delG NR_182091.1:n.1477delG NR_182092.1:n.1477delG NC_000008.11:g.144515205del NC_000008.10:g.145740589del NG_016430.2:g.7625del NG_033083.1:g.2241del NG_033083.2:g.2215del LRG_277:g.7625del LRG_277t1:c.1431del LRG_277p1:p.His478fs - Protein change
- H478fs
- Other names
- -
- Canonical SPDI
- NC_000008.11:144515201:CCCC:CCC
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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.
- -
- 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
|
Jan 4, 2023 | RCV002881062.3 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jan 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Baller-Gerold syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003232688.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His478Thrfs*80) 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). (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:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His478Thrfs*80) 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).
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.