NM_003242.6(TGFBR2):c.263+17A>C AND not specified

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Dec 7, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000435039.4

Allele description [Variation Report for NM_003242.6(TGFBR2):c.263+17A>C]

NM_003242.6(TGFBR2):c.263+17A>C

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.263+17A>C

HGVS:

NC_000003.12:g.30644932A>C
NG_007490.1:g.43431A>C
NM_001024847.3:c.338+17A>C
NM_001407126.1:c.338+17A>C
NM_001407127.1:c.263+17A>C
NM_001407128.1:c.290+17A>C
NM_001407129.1:c.158+17A>C
NM_001407130.1:c.263+17A>C
NM_001407132.1:c.158+17A>C
NM_001407133.1:c.158+17A>C
NM_001407134.1:c.158+17A>C
NM_001407135.1:c.158+17A>C
NM_001407136.1:c.158+17A>C
NM_001407137.1:c.169+21659A>C
NM_001407138.1:c.95-26706A>C
NM_001407139.1:c.338+17A>C
NM_003242.6:c.263+17A>CMANE SELECT
LRG_779t2:c.263+17A>C
LRG_779:g.43431A>C
NC_000003.11:g.30686424A>C
NM_003242.5:c.263+17A>C

Links:

dbSNP: rs34771516

NCBI 1000 Genomes Browser:

rs34771516

Molecular consequence:

NM_001024847.3:c.338+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407126.1:c.338+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407127.1:c.263+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407128.1:c.290+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407129.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407130.1:c.263+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407132.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407133.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407134.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407135.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407136.1:c.158+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407137.1:c.169+21659A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407138.1:c.95-26706A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407139.1:c.338+17A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_003242.6:c.263+17A>C - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000514892	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely benign (Jan 5, 2018)	germline	clinical testing	Citation Link,
SCV001467870	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Dec 7, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12825850, 17319955 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000514892

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely benign
(Jan 5, 2018)

germline

clinical testing

Citation Link,

SCV001467870

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Dec 7, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Higher stromal expression of transforming growth factor-beta type II receptors is associated with poorer prognosis breast tumors.

Barlow J, Yandell D, Weaver D, Casey T, Plaut K.

Breast Cancer Res Treat. 2003 May;79(2):149-59.

PubMed [citation]

PMID:: 12825850

Resequencing of genes for transforming growth factor beta1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy.

McKnight AJ, Savage DA, Patterson CC, Sadlier D, Maxwell AP.

BMC Med Genet. 2007 Feb 23;8:5.

PubMed [citation]

PMID:: 17319955
PMCID:: PMC1808054

Details of each submission

From GeneDx, SCV000514892.4

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001467870.1

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

Description

Variant summary: TGFBR2 c.263+17A>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 250832 control chromosomes. The observed variant frequency is approximately 55- fold 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 benign. c.263+17A>C has been reported in the literature an individual affected with breast cancer (Barlow_2003). This report does not provide unequivocal conclusions about association of the variant with Loeys-Dietz Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as likely benign. Based on the evidence outlined above, the variant was classified as 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: Sep 29, 2024

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