ClinVar Genomic variation as it relates to human health
NM_003242.6(TGFBR2):c.1266A>G (p.Ala422=)
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_003242.6(TGFBR2):c.1266A>G (p.Ala422=)
Variation ID: 36865 Accession: VCV000036865.36
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p24.1 3: 30674116 (GRCh38) [ NCBI UCSC ] 3: 30715608 (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 4, 2013 Apr 20, 2024 Feb 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003242.6:c.1266A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003233.4:p.Ala422= synonymous NM_001024847.3:c.1341A>G NP_001020018.1:p.Ala447= synonymous NM_001407126.1:c.1449A>G NP_001394055.1:p.Ala483= synonymous NM_001407127.1:c.1374A>G NP_001394056.1:p.Ala458= synonymous NM_001407128.1:c.1293A>G NP_001394057.1:p.Ala431= synonymous NM_001407129.1:c.1269A>G NP_001394058.1:p.Ala423= synonymous NM_001407130.1:c.1266A>G NP_001394059.1:p.Ala422= synonymous NM_001407132.1:c.1161A>G NP_001394061.1:p.Ala387= synonymous NM_001407133.1:c.1161A>G NP_001394062.1:p.Ala387= synonymous NM_001407134.1:c.1161A>G NP_001394063.1:p.Ala387= synonymous NM_001407135.1:c.1161A>G NP_001394064.1:p.Ala387= synonymous NM_001407136.1:c.1161A>G NP_001394065.1:p.Ala387= synonymous NM_001407137.1:c.981A>G NP_001394066.1:p.Ala327= synonymous NM_001407138.1:c.906A>G NP_001394067.1:p.Ala302= synonymous NM_001407139.1:c.530-14271A>G intron variant NC_000003.12:g.30674116A>G NC_000003.11:g.30715608A>G NG_007490.1:g.72615A>G LRG_779:g.72615A>G LRG_779t1:c.1341A>G LRG_779p1:p.Ala447= LRG_779t2:c.1266A>G LRG_779p2:p.Ala422= - Protein change
- Other names
- p.A422A:GCA>GCG
- Canonical SPDI
- NC_000003.12:30674115:A:G
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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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0.03115 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00702
Exome Aggregation Consortium (ExAC) 0.00878
The Genome Aggregation Database (gnomAD) 0.02974
Trans-Omics for Precision Medicine (TOPMed) 0.03094
1000 Genomes Project 0.03115
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.03160
1000 Genomes Project 30x 0.03310
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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TGFBR2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1163 | 1190 |
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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Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 14, 2016 | RCV000030547.15 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 26, 2012 | RCV000037731.22 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000370024.15 | |
Benign (1) |
criteria provided, single submitter
|
Jul 7, 2015 | RCV000617140.9 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000253560.27 | |
Benign (1) |
criteria provided, single submitter
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Aug 14, 2021 | RCV001811224.13 | |
Benign (1) |
criteria provided, single submitter
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Aug 13, 2021 | RCV002277110.10 |
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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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000309518.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Oct 26, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000168943.10
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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benign
(Aug 18, 2011)
|
criteria provided, single submitter
Method: clinical testing
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Loeys-Dietz Syndrome
(autosomal unknown)
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000053218.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022 |
Comment:
Converted during submission to Benign.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
Observation 3:
Tissue: Blood
|
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Benign
(Aug 13, 2021)
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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: SCV002566152.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
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Benign
(Jan 31, 2024)
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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
|
Invitae
Accession: SCV000559159.8
First in ClinVar: Dec 06, 2016 Last updated: Feb 14, 2024 |
|
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Benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Thoracic Aortic Aneurysms and Aortic Dissections
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000442891.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Loeys-Dietz Syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000442889.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Loeys-Dietz syndrome 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000442890.3
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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Benign
(Aug 14, 2021)
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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: SCV000884688.3
First in ClinVar: Feb 18, 2019 Last updated: Jan 08, 2022 |
|
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Benign
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Loeys-Dietz syndrome 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004841419.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 1646
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Benign
(Mar 16, 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
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902791.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
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Benign
(Jan 21, 2009)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061393.6
First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 10
|
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Benign
(Jul 07, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000317709.5
First in ClinVar: Oct 02, 2016 Last updated: Apr 13, 2018 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: 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)
Number of individuals with the variant: 1
|
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Benign
(Dec 01, 2022)
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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
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004239742.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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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
HelpTitle | Author | Journal | Year | Link |
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Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders. | Stheneur C | Human mutation | 2008 | PMID: 18781618 |
Text-mined citations for rs2228047 ...
HelpRecord last updated Aug 18, 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.