NM_003238.6(TGFB2):c.52G>T (p.Ala18Ser) AND Loeys-Dietz syndrome 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 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:: RCV001921010.4

Allele description [Variation Report for NM_003238.6(TGFB2):c.52G>T (p.Ala18Ser)]

NM_003238.6(TGFB2):c.52G>T (p.Ala18Ser)

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.52G>T (p.Ala18Ser)

HGVS:

NC_000001.11:g.218346753G>T
NG_027721.2:g.6420G>T
NM_001135599.4:c.52G>T
NM_003238.6:c.52G>TMANE SELECT
NP_001129071.1:p.Ala18Ser
NP_003229.1:p.Ala18Ser
NC_000001.10:g.218520095G>T
NR_138148.2:n.1418G>T
NR_138149.2:n.1418G>T

Protein change:

A18S

Links:

dbSNP: rs886045975

NCBI 1000 Genomes Browser:

rs886045975

Molecular consequence:

NM_001135599.4:c.52G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003238.6:c.52G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_138148.2:n.1418G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.1418G>T - 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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Pnpla1 patatin-like phospholipase domain containing 1 [Mus musculus]
Pnpla1 patatin-like phospholipase domain containing 1 [Mus musculus]
Gene ID:433091

Gene
433091[uid] AND (alive[prop]) (1)
Gene
Rattus norvegicus proteasome (prosome, macropain) 26S subunit, non-ATPase, 10, m...
Rattus norvegicus proteasome (prosome, macropain) 26S subunit, non-ATPase, 10, mRNA (cDNA clone MGC:187342 IMAGE:8369120), complete cds
gi|165970851|gb|BC158584.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002196930	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	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

SCV002196930

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

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

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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, SCV002196930.3

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 18 of the TGFB2 protein (p.Ala18Ser). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TGFB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1415531). This variant has not been reported in the literature in individuals affected with TGFB2-related conditions. 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: Sep 29, 2024

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