ClinVar Genomic variation as it relates to human health
NM_001999.4(FBN2):c.829G>A (p.Val277Ile)
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_001999.4(FBN2):c.829G>A (p.Val277Ile)
Variation ID: 213259 Accession: VCV000213259.52
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q23.3 5: 128446604 (GRCh38) [ NCBI UCSC ] 5: 127782297 (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 Oct 2, 2016 May 12, 2024 Apr 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001999.4:c.829G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001990.2:p.Val277Ile missense NC_000005.10:g.128446604C>T NC_000005.9:g.127782297C>T NG_008750.1:g.96439G>A - Protein change
- V277I
- Other names
- -
- Canonical SPDI
- NC_000005.10:128446603: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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0.00100 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00094
1000 Genomes Project 0.00100
The Genome Aggregation Database (gnomAD), exomes 0.00168
Exome Aggregation Consortium (ExAC) 0.00181
Trans-Omics for Precision Medicine (TOPMed) 0.00190
The Genome Aggregation Database (gnomAD) 0.00210
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00292
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
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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FBN2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
3049 | 3165 |
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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Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jul 30, 2023 | RCV000195579.29 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Apr 7, 2024 | RCV000204651.28 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000514077.34 | |
Uncertain significance (1) |
no assertion criteria provided
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Mar 30, 2017 | RCV000583514.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Jun 14, 2022 | RCV002277516.10 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 11, 2018 | RCV002310778.9 | |
Benign (1) |
criteria provided, single submitter
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Aug 4, 2020 | RCV003891767.1 |
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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Likely benign
(Apr 15, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000594756.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Likely benign
(Jun 13, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610895.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Congenital contractural arachnodactyly
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001136970.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Congenital contractural arachnodactyly
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000452646.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Likely benign
(Nov 10, 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: SCV000250141.12
First in ClinVar: Oct 11, 2015 Last updated: Nov 25, 2023 |
Comment:
See Variant Classification Assertion Criteria.
|
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Likely benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Congenital contractural arachnodactyly
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000261991.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
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Benign
(May 28, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603679.7
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
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Benign
(Aug 04, 2020)
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criteria provided, single submitter
Method: clinical testing
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FBN2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308658.2
First in ClinVar: Oct 02, 2016 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Jun 11, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000317371.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Jun 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Ehlers-Danlos syndrome
Affected status: unknown
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002565980.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
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Likely benign
(Jul 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004029406.1
First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023 |
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Likely benign
(Apr 07, 2024)
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criteria provided, single submitter
Method: clinical testing
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Congenital contractural arachnodactyly
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812742.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
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Likely benign
(Mar 01, 2024)
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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: SCV002545349.11
First in ClinVar: Jul 09, 2022 Last updated: May 12, 2024 |
Comment:
FBN2: BS1
Number of individuals with the variant: 5
|
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Uncertain significance
(Mar 30, 2017)
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no assertion criteria provided
Method: clinical testing
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Loeys-Dietz syndrome
Affected status: yes
Allele origin:
germline
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Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000692231.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799790.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808591.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001926917.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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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 rs146849637 ...
HelpRecord last updated May 19, 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.