Submissions for variant NM_016628.5(WAC):c.381+4_381+7del

dbSNP: rs1564400647

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV000782094	SCV000920565	uncertain significance	not provided	2018-06-06	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001253727	SCV001429580	uncertain significance	DeSanto-Shinawi syndrome due to WAC point mutation	2020-01-09	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
GeneDx	RCV000782094	SCV003918545	pathogenic	not provided	2022-10-10	criteria provided, single submitter	clinical testing	Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV001253727	SCV004032475	likely pathogenic	DeSanto-Shinawi syndrome due to WAC point mutation	2023-03-03	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital	RCV001253727	SCV005324798	likely pathogenic	DeSanto-Shinawi syndrome due to WAC point mutation		criteria provided, single submitter	clinical testing	This variant was identified as de novo. The variant involves the intronic +5 splice site and splice predictors support a deleterious effect. It can be classified as likely pathogenic.
Clinical Genomics Laboratory, Stanford Medicine	RCV001253727	SCV001427241	uncertain significance	DeSanto-Shinawi syndrome due to WAC point mutation	2020-06-26	no assertion criteria provided	clinical testing	The c.381+4_381+7delAGTA variant in the WAC gene was identified de novo in this individual, but has not been previously reported in association with disease.This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/).The c.381+4_381+7delAGTA variant occurs in the 5’ splice site of intron 4 and computational tools predict that this variant causes a loss of the splice site.However, the accuracy of these computational tools is limited.These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the c.381+4_381+7delAGTA variant is uncertain.However, there is suspicion that this variant could be associated with disease due to it being identified de novo in this individual and the predicted impact to splicing. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PS2_Supporting;PM2; PP3]