NM_003238.6(TGFB2):c.302AGG[1] (p.Glu102del) AND Loeys-Dietz syndrome 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV001824431.15

Allele description [Variation Report for NM_003238.6(TGFB2):c.302AGG[1] (p.Glu102del)]

NM_003238.6(TGFB2):c.302AGG[1] (p.Glu102del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_003238.6(TGFB2):c.302AGG[1] (p.Glu102del)

HGVS:

NC_000001.11:g.218347003AGG[1]
NG_027721.2:g.6670AGG[1]
NM_001135599.4:c.302AGG[1]
NM_003238.6:c.302AGG[1]MANE SELECT
NP_001129071.1:p.Glu102del
NP_003229.1:p.Glu102del
NC_000001.10:g.218520345AGG[1]
NC_000001.10:g.218520345_218520347del
NM_003238.3:c.305_307del
NR_138148.2:n.1668AGG[1]
NR_138149.2:n.1668AGG[1]

Protein change:

E102del

Links:

dbSNP: rs1656708526

NCBI 1000 Genomes Browser:

rs1656708526

Molecular consequence:

NM_001135599.4:c.302AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_003238.6:c.302AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_138148.2:n.1668AGG[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.1668AGG[1] - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001409086	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29392890, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001409086

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2022)

germline

clinical testing

PubMed (2)
[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

A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3.

Schepers D, Tortora G, Morisaki H, MacCarrick G, Lindsay M, Liang D, Mehta SG, Hague J, Verhagen J, van de Laar I, Wessels M, Detisch Y, van Haelst M, Baas A, Lichtenbelt K, Braun K, van der Linde D, Roos-Hesselink J, McGillivray G, Meester J, Maystadt I, Coucke P, et al.

Hum Mutat. 2018 May;39(5):621-634. doi: 10.1002/humu.23407. Epub 2018 Mar 6.

PubMed [citation]

PMID:: 29392890
PMCID:: PMC5947146

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, SCV001409086.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 962501). This variant has been observed in individual(s) with clinical features of Loeys-Dietz syndrome (PMID: 29392890). This variant is not present in population databases (gnomAD no frequency). This variant, c.305_307del, results in the deletion of 1 amino acid(s) of the TGFB2 protein (p.Glu102del), but otherwise preserves the integrity of the reading frame.

#	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 8, 2024

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