ClinVar Miner

Submissions for variant NM_001135599.3(TGFB2):c.905dup (p.Asn302fs) (rs863223796)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197799 SCV000250848 pathogenic not provided 2015-05-12 criteria provided, single submitter clinical testing Although the c.821dupA pathogenic variant in the TGFB2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Asparagine 274, changing it to a Lysine, and creating a premature stop codon at position 19 of the new reading frame, denoted p.Asn274LysfsX19. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift pathogenic variants in the TGFB2 gene have been reported in the Human Gene Mutation Database in association with thoracic aortic aneurysms and dissections (Stenson P et al., 2014). Furthermore, the c.821dupA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507174 SCV000605368 pathogenic not specified 2016-12-21 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000197799 SCV000927984 likely pathogenic not provided 2018-10-09 criteria provided, single submitter clinical testing
Invitae RCV001063952 SCV001228823 pathogenic Holt-Oram syndrome 2019-02-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn274Lysfs*19) in the TGFB2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TGFB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 213849). Loss-of-function variants in TGFB2 are known to be pathogenic (PMID: 22772368, 22772371). For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170227 SCV001332787 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2018-07-19 criteria provided, single submitter clinical testing

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