VCV000344652.9 - ClinVar

NM_003242.6(TGFBR2):c.-193G>A

Germline

Classification

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.

(5)

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.

Uncertain significance/Uncertain risk allele

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003242.6(TGFBR2):c.-193G>A

Variation ID: 344652 Accession: VCV000344652.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p24.1 3: 30606691 (GRCh38) [ NCBI UCSC ] 3: 30648183 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Dec 6, 2016	May 1, 2024	Aug 23, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_003242.6:c.-193G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		5 prime UTR
NM_001024847.3:c.-193G>A
NM_001407126.1:c.-193G>A
NM_001407127.1:c.-193G>A
NM_001407130.1:c.-193G>A
NM_001407133.1:c.-476G>A
NM_001407134.1:c.-354G>A
NM_001407135.1:c.-401G>A
NM_001407136.1:c.-486G>A
NM_001407137.1:c.-193G>A
NM_001407138.1:c.-193G>A
NM_001407139.1:c.-193G>A
NC_000003.12:g.30606691G>A
NC_000003.11:g.30648183G>A
NG_007490.1:g.5190G>A
LRG_779:g.5190G>A
LRG_779t1:c.-193G>A
LRG_779t2:c.-193G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:30606690:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00027

The Genome Aggregation Database (gnomAD) 0.00034

1000 Genomes Project 30x 0.00047

Links

ClinGen: CA10615556 dbSNP: rs886058301 VarSome

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
Gene	OMIM	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.
TGFBR2		Some evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1173	1200
LOC129936399	-	-	-	GRCh38	-	10

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.
Loeys-Dietz syndrome	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000285652.6
Marfan syndrome	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000342929.6
Loeys-Dietz syndrome 2	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV000397680.6
Colorectal cancer, hereditary nonpolyposis, type 6 Loeys-Dietz syndrome 2 Malignant tumor of esophagus	Uncertain significance (1)	criteria provided, single submitter	Aug 23, 2021	RCV002487512.1
Diabetic retinopathy	Uncertain risk allele (1)	criteria provided, single submitter	-	RCV004021906.1

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.
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Marfan Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000442821.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Loeys-Dietz Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000442820.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Loeys-Dietz syndrome 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000442822.3 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Uncertain significance (Aug 23, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Malignant tumor of esophagus Loeys-Dietz syndrome 2 Colorectal cancer, hereditary nonpolyposis, type 6 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002785314.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain risk allele (-)	criteria provided, single submitter (K And H Uppaluri Personalized Medicine Clinic Variant Classification And Assertion Criteria Updated V 2) Method: research	Diabetic retinopathy Affected status: unknown Allele origin: unknown	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV005016456.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 30222965‚ 28162229‚ 34572573 Comment: Potent mutations in TGFBR2 gene encodes the transforming growth factor that have been associated with angiogenesis and diabetic retinopathy. More clinical studies are needed for … (more) Potent mutations in TGFBR2 gene encodes the transforming growth factor that have been associated with angiogenesis and diabetic retinopathy. More clinical studies are needed for stronger association. However, more evidence is required to confer the association of this particular variant rs886058301 with diabetic retinopathy. (less)

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 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

Potent mutations in TGFBR2 gene encodes the transforming growth factor that have been associated with angiogenesis and diabetic retinopathy. More clinical studies are needed for stronger association. However, more evidence is required to confer the association of this particular variant rs886058301 with diabetic retinopathy.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain.	Schlecht A	Biomolecules	2021	PMID: 34572573
Computational systems biology approach to identify novel pharmacological targets for diabetic retinopathy.	Platania CBM	Biochemical pharmacology	2018	PMID: 30222965
The Increased Transforming Growth Factor-β Signaling Induced by Diabetes Protects Retinal Vessels.	Dagher Z	The American journal of pathology	2017	PMID: 28162229

Text-mined citations for rs886058301 ...

These 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 May 08, 2024

ClinVar Genomic variation as it relates to human health

NM_003242.6(TGFBR2):c.-193G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs886058301 ...