Submissions for variant NM_152564.5(VPS13B):c.9742+2dup

gnomAD frequency: 0.00002  dbSNP: rs770968105

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001929598	SCV002198641	uncertain significance	Cohen syndrome	2021-09-15	criteria provided, single submitter	clinical testing	This sequence change falls in intron 53 of the VPS13B gene. It does not directly change the encoded amino acid sequence of the VPS13B protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs770968105, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV001929598	SCV002792493	uncertain significance	Cohen syndrome	2022-02-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004743659	SCV005352726	uncertain significance	VPS13B-related disorder	2024-04-09	no assertion criteria provided	clinical testing	The VPS13B c.9742+2dupT variant is predicted to result in an intronic duplication. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.