NM_003242.6(TGFBR2):c.383del (p.Lys128fs) AND Loeys-Dietz syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 10, 2018
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:: RCV000680445.1

Allele description

NM_003242.6(TGFBR2):c.383del (p.Lys128fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.383del (p.Lys128fs)

HGVS:

NC_000003.12:g.30650389del
NG_007490.1:g.48888del
NM_003242.6:c.383delMANE SELECT
NP_001020018.1:p.Lys153fs
NP_003233.4:p.Lys128fs
LRG_779t1:c.458del
LRG_779t2:c.383del
LRG_779:g.48888del
LRG_779p1:p.Lys153fs
LRG_779p2:p.Lys128fs
NC_000003.11:g.30691881del
NC_000003.11:g.30691881delA
NM_001024847.2:c.458del
NM_003242.5:c.383del
NM_003242.5:c.383delA

Protein change:

K128fs

Links:

dbSNP: rs79375991

NCBI 1000 Genomes Browser:

rs79375991

Molecular consequence:

NM_003242.6:c.383del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Loeys-Dietz syndrome (LDS)
Identifiers:: MONDO: MONDO:0018954; MedGen: C2697932; OMIM: PS609192

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000807818	GeneID Lab - Advanced Molecular Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 10, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000807818

GeneID Lab - Advanced Molecular Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 10, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Latin American	germline	no	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneID Lab - Advanced Molecular Diagnostics, SCV000807818.1

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

Description

This variant results in an amino acid alteration replacing a lysine (K) with a serine (S) at position 128 creating a premature stop signal in the new reading frame noted as p K128Sfs*35. The substitution is predicted to result in a non-functional TGFBR2 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH, Bethesda MD), but it has been described in 3478 alleles out of 85936, in the ExAC database, all of them belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 18, 2022

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