NM_003238.6(TGFB2):c.59G>A (p.Ser20Asn) AND Loeys-Dietz syndrome 4

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 13, 2019
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:: RCV001824402.16

Allele description [Variation Report for NM_003238.6(TGFB2):c.59G>A (p.Ser20Asn)]

NM_003238.6(TGFB2):c.59G>A (p.Ser20Asn)

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.59G>A (p.Ser20Asn)

HGVS:

NC_000001.11:g.218346760G>A
NG_027721.2:g.6427G>A
NM_001135599.4:c.59G>A
NM_003238.6:c.59G>AMANE SELECT
NP_001129071.1:p.Ser20Asn
NP_003229.1:p.Ser20Asn
NC_000001.10:g.218520102G>A
NM_003238.3:c.59G>A
NR_138148.2:n.1425G>A
NR_138149.2:n.1425G>A

Protein change:

S20N

Links:

dbSNP: rs1656695125

NCBI 1000 Genomes Browser:

rs1656695125

Molecular consequence:

NM_001135599.4:c.59G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003238.6:c.59G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_138148.2:n.1425G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.1425G>A - 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
SCV001203698	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004228634	GenomeConnect - Invitae Patient Insights Network	no classification provided	not provided	unknown	phenotyping only

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001203698

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 2019)

germline

clinical testing

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

SCV004228634

GenomeConnect - Invitae Patient Insights Network

no classification provided

not provided

unknown

phenotyping only

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
not provided	unknown	unknown	1	not provided	not provided	1	not provided	phenotyping only

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, SCV001203698.6

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TGFB2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 20 of the TGFB2 protein (p.Ser20Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine.

#	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

From GenomeConnect - Invitae Patient Insights Network, SCV004228634.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	phenotyping only	not provided

Description

Variant interpreted as Uncertain significance and reported on 12-12-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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

Last Updated: Nov 3, 2024

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