Submissions for variant NM_152564.5(VPS13B):c.7660G>C (p.Val2554Leu)

gnomAD frequency: 0.00014  dbSNP: rs202226215

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000516628	SCV000616275	uncertain significance	not provided	2018-03-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083496	SCV000755401	benign	Cohen syndrome	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000516628	SCV001751750	likely benign	not provided	2020-08-26	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001083496	SCV002496028	uncertain significance	Cohen syndrome	2021-03-30	criteria provided, single submitter	clinical testing	VPS13B NM_017890.4 exon 42 p.Val2579Leu (c.7735G>C): This variant has not been reported in the literature but is present in 0.1% (20/15276) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/8-99778912-G-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:448878). This variant amino acid Leucine (Leu) is present in several species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics	RCV002404336	SCV002672133	benign	Inborn genetic diseases	2017-06-23	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
PreventionGenetics, part of Exact Sciences	RCV003915464	SCV004734429	likely benign	VPS13B-related disorder	2021-05-05	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).