NM_003242.6(TGFBR2):c.556T>A (p.Phe186Ile) AND Loeys-Dietz syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 5, 2023
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:: RCV004000768.2

Allele description [Variation Report for NM_003242.6(TGFBR2):c.556T>A (p.Phe186Ile)]

NM_003242.6(TGFBR2):c.556T>A (p.Phe186Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.556T>A (p.Phe186Ile)

HGVS:

NC_000003.12:g.30671739T>A
NG_007490.1:g.70238T>A
NM_001024847.3:c.631T>A
NM_001407126.1:c.739T>A
NM_001407127.1:c.664T>A
NM_001407128.1:c.583T>A
NM_001407129.1:c.559T>A
NM_001407130.1:c.556T>A
NM_001407132.1:c.451T>A
NM_001407133.1:c.451T>A
NM_001407134.1:c.451T>A
NM_001407135.1:c.451T>A
NM_001407136.1:c.451T>A
NM_001407137.1:c.271T>A
NM_001407138.1:c.196T>A
NM_003242.6:c.556T>AMANE SELECT
NP_001020018.1:p.Phe211Ile
NP_001020018.1:p.Phe211Ile
NP_001394055.1:p.Phe247Ile
NP_001394056.1:p.Phe222Ile
NP_001394057.1:p.Phe195Ile
NP_001394058.1:p.Phe187Ile
NP_001394059.1:p.Phe186Ile
NP_001394061.1:p.Phe151Ile
NP_001394062.1:p.Phe151Ile
NP_001394063.1:p.Phe151Ile
NP_001394064.1:p.Phe151Ile
NP_001394065.1:p.Phe151Ile
NP_001394066.1:p.Phe91Ile
NP_001394067.1:p.Phe66Ile
NP_003233.4:p.Phe186Ile
LRG_779t1:c.631T>A
LRG_779t2:c.556T>A
LRG_779:g.70238T>A
LRG_779p1:p.Phe211Ile
LRG_779p2:p.Phe186Ile
NC_000003.11:g.30713231T>A
NM_001024847.2:c.631T>A
NM_003242.5:c.556T>A

Protein change:

F151I

Links:

dbSNP: rs368346624

NCBI 1000 Genomes Browser:

rs368346624

Molecular consequence:

NM_001024847.3:c.631T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.739T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.664T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.583T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.559T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.556T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.451T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.451T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.451T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.451T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.451T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.271T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.196T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.556T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Loeys-Dietz syndrome 2 (LDS2)
Synonyms:: Loeys-Dietz syndrome type 1B; MARFAN SYNDROME, TYPE II; Loeys-Dietz syndrome type 2B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012427; MedGen: C2674574; Orphanet: 558; OMIM: 610168

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004839169	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Sep 5, 2023)	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

SCV004839169

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Sep 5, 2023)

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
not provided	germline	unknown	1	not provided	not provided	108544	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 All of Us Research Program, National Institutes of Health, SCV004839169.1

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

Description

This missense variant replaces phenylalanine with isoleucine at codon 186 of the TGFBR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31404 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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