Submissions for variant NM_206538.4(EMC10):c.287del (p.Gly96fs)

dbSNP: rs770255014

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	RCV001374394	SCV002507293	pathogenic	Neurodevelopmental disorder with dysmorphic facies and variable seizures		criteria provided, single submitter	clinical testing	The detected change is listed in gnomAD with a frequency of 0.002542% (6/236018) (as of May 12, 2022). It is not reported in the dbSNP database (dbSNP150, as of May 12, 2022). The change has already been described in the literature as a recurrent variant in patients with developmental disorders and dysmorphism (Shao et al., 2021; Umair et al., 2020). In the case of stop or nonsense variants in a gene matching the phenotype, there is also a high probability of pathogenetic relevance. Based on the current state of knowledge, the variant can be classified as a pathogenic variant (ACMG criteria).
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV002508800	SCV002818242	pathogenic	not provided	2022-12-17	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001374394	SCV004046305	pathogenic	Neurodevelopmental disorder with dysmorphic facies and variable seizures		criteria provided, single submitter	clinical testing	This frameshifting variant in exon 3 of 7 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been previously reported as a homozygous change in individuals with Neurodevelopmental disorder with dysmorphic facies and variable seizures (NEDDFAS) (PMID: 33531666, 35684946). The c.287del (p.Gly96AlafsTer9) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.003% (6/236018) and is absent in the homozygous state; thus it is presumed to be rare. Based on the available evidence, the c.287del (p.Gly96AlafsTer9) variant is classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001374394	SCV004805413	uncertain significance	Neurodevelopmental disorder with dysmorphic facies and variable seizures	2024-03-25	criteria provided, single submitter	research
Christopher A. Walsh Laboratory, Boston Children's Hospital	RCV001270149	SCV001448246	uncertain significance	Intellectual disability		no assertion criteria provided	research
OMIM	RCV001374394	SCV001571245	pathogenic	Neurodevelopmental disorder with dysmorphic facies and variable seizures	2022-09-06	no assertion criteria provided	literature only