Submissions for variant NM_001291303.3(FAT4):c.6094A>G (p.Thr2032Ala)

gnomAD frequency: 0.00015  dbSNP: rs147314754

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000489561	SCV000577470	uncertain significance	not specified	2017-03-28	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the FAT4 gene. The T2032A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T2032A variant is observed in 20/66732 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T2032A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position where amino acids with similar properties to Threonine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001700194	SCV002370621	likely benign	not provided	2023-12-30	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001700194	SCV003833972	uncertain significance	not provided	2021-02-05	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis	RCV003458201	SCV004177063	uncertain significance	Hennekam lymphangiectasia-lymphedema syndrome 2	2023-09-29	criteria provided, single submitter	clinical testing	The FAT4 c.6094A>G (p.Thr2032Ala) variant was identified at a near heterozygous allelic fraction. This variant, to our knowledge, has not been reported in the literature. This variant has been reported in the ClinVar database as a variant of uncertain significance by multiple submitters and likely benign variant by one submitter (ClinVar ID: 426899). Computational predictors are uncertain as to the impact of this variant on FAT4 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
Clinical Genetics, Academic Medical Center	RCV001700194	SCV001919072	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700194	SCV001964739	uncertain significance	not provided		no assertion criteria provided	clinical testing