NM_003238.6(TGFB2):c.194dup (p.Glu66fs) AND Loeys-Dietz syndrome 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 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:: RCV001824454.13

Allele description [Variation Report for NM_003238.6(TGFB2):c.194dup (p.Glu66fs)]

NM_003238.6(TGFB2):c.194dup (p.Glu66fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_003238.6(TGFB2):c.194dup (p.Glu66fs)

HGVS:

NC_000001.11:g.218346895dup
NG_027721.2:g.6562dup
NM_001135599.4:c.194dup
NM_003238.6:c.194dupMANE SELECT
NP_001129071.1:p.Glu66fs
NP_003229.1:p.Glu66fs
NC_000001.10:g.218520231_218520232insC
NC_000001.10:g.218520237dup
NM_003238.3:c.194dupC
NR_138148.2:n.1560dup
NR_138149.2:n.1560dup

Protein change:

E66fs

Links:

dbSNP: rs2102527595

NCBI 1000 Genomes Browser:

rs2102527595

Molecular consequence:

NM_001135599.4:c.194dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003238.6:c.194dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_138148.2:n.1560dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.1560dup - 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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tRNA 2'-phosphotransferase 1 isoform 3 [Homo sapiens]
tRNA 2'-phosphotransferase 1 isoform 3 [Homo sapiens]
gi|238550149|ref|NP_001153861.1|

Protein
Homo sapiens hypothetical protein FLJ11155 (FLJ11155), mRNA
Homo sapiens hypothetical protein FLJ11155 (FLJ11155), mRNA
gi|8922902|ref|NM_018342.1|

Nucleotide
AGENCOURT_6709745 NIH_MGC_116 Homo sapiens cDNA clone IMAGE:5760100 5', mRNA seq...
AGENCOURT_6709745 NIH_MGC_116 Homo sapiens cDNA clone IMAGE:5760100 5', mRNA sequence
gi|19374333|gnl|dbEST|11607379|gb|B 54.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589974	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22772368, 22772371, 30739908, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589974

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2023)

germline

clinical testing

PubMed (4)
[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

Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm.

Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, et al.

Nat Genet. 2012 Jul 8;44(8):922-7. doi: 10.1038/ng.2349.

PubMed [citation]

PMID:: 22772368
PMCID:: PMC3616632

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome.

Boileau C, Guo DC, Hanna N, Regalado ES, Detaint D, Gong L, Varret M, Prakash SK, Li AH, d'Indy H, Braverman AC, Grandchamp B, Kwartler CS, Gouya L, Santos-Cortez RL, Abifadel M, Leal SM, Muti C, Shendure J, Gross MS, Rieder MJ, Vahanian A, et al.

Nat Genet. 2012 Jul 8;44(8):916-21. doi: 10.1038/ng.2348.

PubMed [citation]

PMID:: 22772371
PMCID:: PMC4033668

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589974.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1075270). This variant has not been reported in the literature in individuals affected with TGFB2-related conditions. This sequence change creates a premature translational stop signal (p.Glu66Glyfs*68) in the TGFB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGFB2 are known to be pathogenic (PMID: 22772368, 22772371, 30739908). This variant is not present in population databases (gnomAD no frequency).

#	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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