NM_003242.6(TGFBR2):c.383dup (p.Pro129fs) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004017749.2

Allele description [Variation Report for NM_003242.6(TGFBR2):c.383dup (p.Pro129fs)]

NM_003242.6(TGFBR2):c.383dup (p.Pro129fs)

Gene:

TGFBR2:transforming growth factor beta receptor 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.383dup (p.Pro129fs)

HGVS:

NC_000003.12:g.30650389dup
NG_007490.1:g.48888dup
NM_001024847.3:c.458dup
NM_001407126.1:c.458dup
NM_001407127.1:c.383dup
NM_001407128.1:c.410dup
NM_001407129.1:c.278dup
NM_001407130.1:c.383dup
NM_001407132.1:c.278dup
NM_001407133.1:c.278dup
NM_001407134.1:c.278dup
NM_001407135.1:c.278dup
NM_001407136.1:c.278dup
NM_001407139.1:c.458dup
NM_003242.6:c.383dupMANE SELECT
NP_001020018.1:p.Pro154Alafs
NP_001020018.1:p.Pro154fs
NP_001394055.1:p.Pro154Alafs
NP_001394056.1:p.Pro129Alafs
NP_001394057.1:p.Pro138Alafs
NP_001394058.1:p.Pro94Alafs
NP_001394059.1:p.Pro129Alafs
NP_001394061.1:p.Pro94Alafs
NP_001394062.1:p.Pro94Alafs
NP_001394063.1:p.Pro94Alafs
NP_001394064.1:p.Pro94Alafs
NP_001394065.1:p.Pro94Alafs
NP_001394068.1:p.Pro154Alafs
NP_003233.4:p.Pro129fs
LRG_779t1:c.458dup
LRG_779t2:c.383dup
LRG_779:g.48888dup
LRG_779p1:p.Pro154fs
LRG_779p2:p.Pro129fs
NC_000003.11:g.30691871_30691872insA
NC_000003.11:g.30691881dup
NC_000003.12:g.30650389_30650390insA
NM_001024847.2:c.458dup
NM_003242.5:c.383dup
NM_003242.5:c.383dupA
NM_003242.6:c.383dupAMANE SELECT

Protein change:

P129fs

Links:

dbSNP: rs79375991

NCBI 1000 Genomes Browser:

rs79375991

Molecular consequence:

NM_001024847.3:c.458dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407126.1:c.458dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407127.1:c.383dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407128.1:c.410dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407129.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407130.1:c.383dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407132.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407133.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407134.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407135.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407136.1:c.278dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407139.1:c.458dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003242.6:c.383dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848097	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Nov 3, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26948038, 23585368, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848097

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Nov 3, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Successful Single-Stage Operation for Loeys-Dietz Syndrome With Critical Coarctation of the Descending Aorta in a Young Adult.

Wei S, Huang X, Hu S, Yang Y, Liu F.

Can J Cardiol. 2016 Oct;32(10):1260.e15-1260.e17. doi: 10.1016/j.cjca.2015.11.015. Epub 2015 Nov 23.

PubMed [citation]

PMID:: 26948038

Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer.

Smith CG, Naven M, Harris R, Colley J, West H, Li N, Liu Y, Adams R, Maughan TS, Nichols L, Kaplan R, Wagner MJ, McLeod HL, Cheadle JP.

Hum Mutat. 2013 Jul;34(7):1026-34. doi: 10.1002/humu.22333. Epub 2013 May 20.

PubMed [citation]

PMID:: 23585368

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848097.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.383dupA (p.Pro129fs) variant in TGFBR2 has not been previously reported in individuals with Loeys-Dietz Syndrome. This variant has been identified in 50/74078 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs756007977), though the ability of these studies to accurately detect indels may be limited, as this variant occurs within a sequence of A repeats. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 129 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. While loss of function variants in TGFBR2 have been reported in Loeys-Dietz syndrome, the location of this variant in a sequence of mononucleotide repeats, as well as the prevalence of this variant in population databases and absence in affected individuals provides conflicting evidence of pathogenicity. In summary, the clinical significance of the p.Pro129fs variant is uncertain.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine