Submissions for variant NM_003238.6(TGFB2):c.114G>A (p.Glu38=)

gnomAD frequency: 0.00087  dbSNP: rs149215818

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000200359	SCV000250832	benign	not specified	2014-08-26	criteria provided, single submitter	clinical testing	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.
Ambry Genetics	RCV000769554	SCV000319458	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000358235	SCV000354236	benign	Loeys-Dietz syndrome 4	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000358235	SCV000559140	benign	Loeys-Dietz syndrome 4	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590091	SCV000698187	benign	not provided	2017-07-14	criteria provided, single submitter	clinical testing	Variant summary: The TGFB2 c.114G>A (p.Glu38Glu) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 405/121312 control chromosomes (3 homozygotes) from ExAC, predominantly observed in the South Asian subpopulation at a frequency of 0.013931 (230/16510). This frequency is about 1114 times the estimated maximal expected allele frequency of a pathogenic TGFB2 variant (0.0000125), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories (via ClinVar) have classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660310	SCV000782349	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000358235	SCV000884680	benign	Loeys-Dietz syndrome 4	2023-04-17	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769554	SCV000900950	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-03-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277541	SCV002566111	benign	Ehlers-Danlos syndrome	2022-05-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000358235	SCV002807984	benign	Loeys-Dietz syndrome 4	2021-10-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590091	SCV004125636	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	TGFB2: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000590091	SCV005263728	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000200359	SCV001809397	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000200359	SCV001932935	benign	not specified		no assertion criteria provided	clinical testing