NM_003238.6(TGFB2):c.143T>G (p.Leu48Arg) AND Loeys-Dietz syndrome 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 8, 2020
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:: RCV001824351.15

Allele description [Variation Report for NM_003238.6(TGFB2):c.143T>G (p.Leu48Arg)]

NM_003238.6(TGFB2):c.143T>G (p.Leu48Arg)

Gene:

TGFB2:transforming growth factor beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_003238.6(TGFB2):c.143T>G (p.Leu48Arg)

HGVS:

NC_000001.11:g.218346844T>G
NG_027721.2:g.6511T>G
NM_001135599.4:c.143T>G
NM_003238.6:c.143T>GMANE SELECT
NP_001129071.1:p.Leu48Arg
NP_003229.1:p.Leu48Arg
NC_000001.10:g.218520186T>G
NM_003238.3:c.143T>G
NM_003238.4:c.143T>G
NR_138148.2:n.1509T>G
NR_138149.2:n.1509T>G

Protein change:

L48R

Links:

dbSNP: rs1553292088

NCBI 1000 Genomes Browser:

rs1553292088

Molecular consequence:

NM_001135599.4:c.143T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003238.6:c.143T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_138148.2:n.1509T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.1509T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Loeys-Dietz syndrome 4 (LDS4)
Synonyms:: ANEURYSM, AORTIC AND CEREBRAL, WITH ARTERIAL TORTUOSITY AND SKELETAL MANIFESTATIONS
Identifiers:: MONDO: MONDO:0013897; MedGen: C3553762; OMIM: 614816

Recent activity

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UI-M-DJ1-btu-f-05-0-UI.s1 NIH_BMAP_DJ1 Mus musculus cDNA clone UI-M-DJ1-btu-f-05...
UI-M-DJ1-btu-f-05-0-UI.s1 NIH_BMAP_DJ1 Mus musculus cDNA clone UI-M-DJ1-btu-f-05-0-UI 3', mRNA sequence
gi|23623134|gnl|dbEST|14161709|gb|B 66.1|

Nucleotide
Sisyrinchieae RNA polymerase beta' subunit (rpoC1) gene, partial cds; chloroplas...
Sisyrinchieae RNA polymerase beta' subunit (rpoC1) gene, partial cds; chloroplast.
PopSet: 339740984

PopSet
Med14 mediator complex subunit 14 [Rattus norvegicus]
Med14 mediator complex subunit 14 [Rattus norvegicus]
Gene ID:317343

Gene
AUNIP aurora kinase A and ninein interacting protein [Homo sapiens]
AUNIP aurora kinase A and ninein interacting protein [Homo sapiens]
Gene ID:79000

Gene
Gene Links for Protein (Select 13128990) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001544042	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 8, 2020)	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

SCV001544042

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 8, 2020)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001544042.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TGFB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 520195). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 48 of the TGFB2 protein (p.Leu48Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine.

#	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: Oct 26, 2024

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