This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory as a de novo finding in a 9-year-old female with intellectual disability, dysmorphic features, hyperextensibility, hirsutism, callosal dysgenesis.
ClinVar Genomic variation as it relates to human health
NM_001374828.1(ARID1B):c.6145C>T (p.Arg2049Ter)
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.
(13)
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/Likely pathogenic
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001374828.1(ARID1B):c.6145C>T (p.Arg2049Ter)
Variation ID: 488678 Accession: VCV000488678.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q25.3 6: 157206917 (GRCh38) [ NCBI UCSC ] 6: 157528051 (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 13, 2018 Jun 17, 2024 Dec 11, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001374828.1:c.6145C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361757.1:p.Arg2049Ter nonsense NM_001363725.2:c.3646C>T NP_001350654.1:p.Arg1216Ter nonsense NM_001371656.1:c.6025C>T NP_001358585.1:p.Arg2009Ter nonsense NM_001374820.1:c.6025C>T NP_001361749.1:p.Arg2009Ter nonsense NM_017519.3:c.5986C>T NP_059989.3:p.Arg1996Ter nonsense NM_020732.3:c.5776C>T NP_065783.3:p.Arg1926Ter nonsense NC_000006.12:g.157206917C>T NC_000006.11:g.157528051C>T NG_066624.1:g.435892C>T - Protein change
- R1926*, R1913*, R1216*, R1996*, R2009*, R2049*
- Other names
- -
- Canonical SPDI
- NC_000006.12:157206916: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
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. |
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| ARID1B | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1899 | 2251 | |
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/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 11, 2023 | RCV000578816.12 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 13, 2017 | RCV000622953.5 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Sep 27, 2022 | RCV000625417.13 | |
|
ARID1B-related BAFopathy
|
Pathogenic (1) |
criteria provided, single submitter
|
Jun 10, 2021 | RCV001533032.4 |
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
(Mar 30, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Coffin-Siris syndrome 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745308.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Coffin-Siris syndrome 1
Affected status: yes
Allele origin:
unknown
|
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn
Accession: SCV001433045.1
First in ClinVar: Sep 24, 2020 Last updated: Sep 24, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Hypopigmentation of the skin (present) , Elbow hypertrichosis (present) , Hypertrichosis (present) , Horizontal eyebrow (present) , Full cheeks (present) , Facial hypertrichosis (present) , … (more)
Hypopigmentation of the skin (present) , Elbow hypertrichosis (present) , Hypertrichosis (present) , Horizontal eyebrow (present) , Full cheeks (present) , Facial hypertrichosis (present) , Broad thumb (present) , Abnormality of the philtrum (present) , Nevus (present) , Low anterior hairline (present) , Low posterior hairline (present) , Muscular hypotonia (present) , Soft, doughy skin (present) , Unilateral strabismus (present) , Lumbar hypertrichosis (present) , Thick lower lip vermilion (present) , Thick eyebrow (present) , Retractile testis (present) (less)
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Pathogenic
(Jun 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
ARID1B-related BAFopathy
Affected status: yes
Allele origin:
de novo
|
Baylor Genetics
Accession: SCV001748851.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
|
|
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Pathogenic
(Jul 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Coffin-Siris syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002054294.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
|
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Pathogenic
(Sep 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Coffin-Siris syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV002578175.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Clinical Features:
Delayed speech and language development (present) , Seizure (present) , Hypertrichosis (present)
Sex: male
Tissue: Blood
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Pathogenic
(Sep 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Coffin-Siris syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Baylor Genetics
Accession: SCV000807357.2
First in ClinVar: Apr 20, 2018 Last updated: Dec 11, 2022 |
Comment:
This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory as a de novo finding in … (more)
This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory as a de novo finding in a 9-year-old female with intellectual disability, dysmorphic features, hyperextensibility, hirsutism, callosal dysgenesis. (less)
|
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Pathogenic
(Apr 13, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000742414.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Neurodevelopmental delay (present) , Muscular hypotonia (present) , Gastroesophageal reflux (present) , Laryngomalacia (present) , Dysphagia (present) , Aspiration pneumonia (present) , Joint laxity (present) … (more)
Neurodevelopmental delay (present) , Muscular hypotonia (present) , Gastroesophageal reflux (present) , Laryngomalacia (present) , Dysphagia (present) , Aspiration pneumonia (present) , Joint laxity (present) , Bruising susceptibility (present) , Plagiocephaly (present) , Low anterior hairline (present) , Square face (present) , Highly arched eyebrow (present) , Wide nasal bridge (present) , Downturned corners of mouth (present) , Long philtrum (present) , Widely spaced teeth (present) , Prominent fingertip pads (present) , Broad thumb (present) , Abnormality of the gingiva (present) (less)
Sex: female
Ethnicity/Population group: Hispanic
|
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Pathogenic
(Jun 13, 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: SCV000680499.4
First in ClinVar: Feb 13, 2018 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 324 amino acids are lost, and other loss-of-function variants have been … (more)
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 324 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25533962, 28135719, 28191890, 31618753, 31526516, 31785789, 27535533, 27474218, 31530938) (less)
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Likely pathogenic
(Oct 05, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
de novo
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV004026366.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
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Pathogenic
(Dec 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004294428.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1926*) in the ARID1B gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg1926*) in the ARID1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 324 amino acid(s) of the ARID1B protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Coffin-Siris syndrome (PMID: 27474218, 31618753). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 488678). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Oct 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Coffin-Siris syndrome 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745860.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001959183.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
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Pathogenic
(Apr 14, 2022)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare
Accession: SCV004175127.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
Clinical Features:
seizure (present) , global developmental delay (present) , behavioral abnormality (present) , abnormal facial shape (present) , Feeding difficulties (present)
Age: 0-9 years
Sex: female
Ethnicity/Population group: South East Asian
Geographic origin: Bangladesh
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| click to load more click to collapse | |||||
Comment:
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 324 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25533962, 28135719, 28191890, 31618753, 31526516, 31785789, 27535533, 27474218, 31530938)
Comment:
This sequence change creates a premature translational stop signal (p.Arg1926*) in the ARID1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 324 amino acid(s) of the ARID1B protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Coffin-Siris syndrome (PMID: 27474218, 31618753). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 488678). For these reasons, this variant has been classified as Pathogenic.
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 nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory as a de novo finding in a 9-year-old female with intellectual disability, dysmorphic features, hyperextensibility, hirsutism, callosal dysgenesis.
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 324 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25533962, 28135719, 28191890, 31618753, 31526516, 31785789, 27535533, 27474218, 31530938)
Comment:
This sequence change creates a premature translational stop signal (p.Arg1926*) in the ARID1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 324 amino acid(s) of the ARID1B protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Coffin-Siris syndrome (PMID: 27474218, 31618753). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 488678). For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Genotype-phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing. | Ziats MN | Pediatric research | 2020 | PMID: 31618753 |
| ARID1B mutations are the major genetic cause of corpus callosum anomalies in patients with intellectual disability. | Mignot C | Brain : a journal of neurology | 2016 | PMID: 27474218 |
| ARID1B-mediated disorders: Mutations and possible mechanisms. | Sim JC | Intractable & rare diseases research | 2015 | PMID: 25674384 |
| Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. | Soden SE | Science translational medicine | 2014 | PMID: 25473036 |
| Coffin-Siris syndrome is a SWI/SNF complex disorder. | Tsurusaki Y | Clinical genetics | 2014 | PMID: 23815551 |
| Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. | Santen GW | Human mutation | 2013 | PMID: 23929686 |
| A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. | Wieczorek D | Human molecular genetics | 2013 | PMID: 23906836 |
| Topological characteristics of helical repeat proteins. | Groves MR | Current opinion in structural biology | 1999 | PMID: 10361086 |
Text-mined citations for rs1554237658 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.