NM_003242.6(TGFBR2):c.4G>T (p.Gly2Cys) AND not specified

Germline classification:: Likely benign (1 submission)
Last evaluated:: May 24, 2021
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:: RCV001526891.2

Allele description [Variation Report for NM_003242.6(TGFBR2):c.4G>T (p.Gly2Cys)]

NM_003242.6(TGFBR2):c.4G>T (p.Gly2Cys)

Gene:

TGFBR2:transforming growth factor beta receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.4G>T (p.Gly2Cys)

HGVS:

NC_000003.12:g.30606887G>T
NG_007490.1:g.5386G>T
NM_001024847.3:c.4G>T
NM_001407126.1:c.4G>T
NM_001407127.1:c.4G>T
NM_001407130.1:c.4G>T
NM_001407133.1:c.-280G>T
NM_001407134.1:c.-158G>T
NM_001407135.1:c.-205G>T
NM_001407136.1:c.-290G>T
NM_001407137.1:c.4G>T
NM_001407138.1:c.4G>T
NM_001407139.1:c.4G>T
NM_003242.6:c.4G>TMANE SELECT
NP_001020018.1:p.Gly2Cys
NP_001020018.1:p.Gly2Cys
NP_001394055.1:p.Gly2Cys
NP_001394056.1:p.Gly2Cys
NP_001394059.1:p.Gly2Cys
NP_001394066.1:p.Gly2Cys
NP_001394067.1:p.Gly2Cys
NP_001394068.1:p.Gly2Cys
NP_003233.4:p.Gly2Cys
LRG_779t1:c.4G>T
LRG_779t2:c.4G>T
LRG_779:g.5386G>T
LRG_779p1:p.Gly2Cys
LRG_779p2:p.Gly2Cys
NC_000003.11:g.30648379G>T
NM_001024847.2:c.4G>T
NM_003242.5:c.4G>T

Protein change:

G2C

Links:

dbSNP: rs565502802

NCBI 1000 Genomes Browser:

rs565502802

Molecular consequence:

NM_001024847.3:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407139.1:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.4G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001737637	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (May 24, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001737637

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(May 24, 2021)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737637.1

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

Description

Variant summary: TGFBR2 c.4G>T (p.Gly2Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.9e-05 in 219764 control chromosomes, predominantly at a frequency of 0.00064 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 205 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFBR2 causing Loeys-Dietz Syndrome phenotype (3.1e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.4G>T in individuals affected with Loeys-Dietz Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

#	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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