Submissions for variant NM_003242.6(TGFBR2):c.1548G>A (p.Thr516=)

gnomAD frequency: 0.00021  dbSNP: rs140662877

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000230654	SCV000287922	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000230654	SCV000317730	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-06-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
GeneDx	RCV000858396	SCV000519023	likely benign	not provided	2021-03-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000430304	SCV000920295	benign	not specified	2018-05-29	criteria provided, single submitter	clinical testing	Variant summary: TGFBR2 c.1548G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 0.00014 in 276692 control chromosomes (gnomAD). The observed variant frequency is approximately 113-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TGFBR2 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1548G>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV000230654	SCV001358815	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-03-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277589	SCV002566155	likely benign	Ehlers-Danlos syndrome	2019-10-01	criteria provided, single submitter	clinical testing