ClinVar Genomic variation as it relates to human health
NM_003072.5(SMARCA4):c.2716C>T (p.Arg906Cys)
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.
Likely pathogenic(1); Uncertain significance(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003072.5(SMARCA4):c.2716C>T (p.Arg906Cys)
Variation ID: 421281 Accession: VCV000421281.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11021824 (GRCh38) [ NCBI UCSC ] 19: 11132500 (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 27, 2017 Mar 4, 2023 Jul 19, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003072.5:c.2716C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003063.2:p.Arg906Cys missense NM_001387283.1:c.2716C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001374212.1:p.Arg906Cys missense NM_001128844.3:c.2716C>T NP_001122316.1:p.Arg906Cys missense NM_001128845.2:c.2716C>T NP_001122317.1:p.Arg906Cys missense NM_001128846.2:c.2716C>T NP_001122318.1:p.Arg906Cys missense NM_001128847.4:c.2716C>T NP_001122319.1:p.Arg906Cys missense NM_001128848.2:c.2716C>T NP_001122320.1:p.Arg906Cys missense NM_001128849.3:c.2716C>T NP_001122321.1:p.Arg906Cys missense NM_001374457.1:c.2716C>T NP_001361386.1:p.Arg906Cys missense NR_164683.1:n.3006C>T non-coding transcript variant NC_000019.10:g.11021824C>T NC_000019.9:g.11132500C>T NG_011556.3:g.65893C>T LRG_878:g.65893C>T LRG_878t1:c.2716C>T LRG_878p1:p.Arg906Cys - Protein change
- R906C
- Other names
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- Canonical SPDI
- NC_000019.10:11021823: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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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
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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SMARCA4 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5565 | 5588 |
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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jul 19, 2021 | RCV000484228.17 | |
Uncertain significance (2) |
criteria provided, single submitter
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Jul 15, 2021 | RCV001253766.11 |
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 25, 2020)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001471845.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The SMARCA4 c.2716C>T; p.Arg906Cys variant (rs898406635), to our knowledge, is not reported in the medical literature as a germline variant but has been reported as … (more)
The SMARCA4 c.2716C>T; p.Arg906Cys variant (rs898406635), to our knowledge, is not reported in the medical literature as a germline variant but has been reported as a somatic variant in at least 2 individuals with different cancers (rectum and head and neck squamous cell carcinoma) (COSMIC: COSV60811731 and Lechner 2013). This variant is also reported in ClinVar (Variation ID: 421281) but is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 906 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the c.2716C>T variant is uncertain at this time. (less)
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Uncertain significance
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 16
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002056184.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
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Likely pathogenic
(Jul 19, 2021)
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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: SCV000570429.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not … (more)
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24658002, 23718828) (less)
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Uncertain significance
(Aug 08, 2019)
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no assertion criteria provided
Method: clinical testing
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Intellectual disability, autosomal dominant 16
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Clinical Genomics Program, Stanford Medicine
Accession: SCV001427070.1
First in ClinVar: Aug 16, 2020 Last updated: Aug 16, 2020 |
Comment:
The p.Arg906Cys variant in the SMARCA4 gene was identified de novo in this individual, and has been previously reported de novo in 1 individual with … (more)
The p.Arg906Cys variant in the SMARCA4 gene was identified de novo in this individual, and has been previously reported de novo in 1 individual with neurological features (GeneDx, personal communication, July 25, 2019). This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The SMARCA4 gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. Computational tools predict that p.Arg906Cys is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Arg906Cys variant is uncertain; however, there is suspicion that this variant could be associated with CoffinSiris syndrome due to the previous identification of this variant de novo in an individual with neurologic disease and the predicted impact to the protein. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PS2_Supporting, PM2, PP2, PP3] (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs898406635 ...
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.