Submissions for variant NM_004247.4(EFTUD2):c.1058+1G>A

dbSNP: rs1085307647

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000488992	SCV000576932	pathogenic	not provided	2023-05-18	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34218205, 32799722, 36909054)
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853362	SCV000996230	pathogenic	Mandibulofacial dysostosis-microcephaly syndrome	2018-12-28	criteria provided, single submitter	clinical testing	This variant affects the canonical splice donor site of intron 12 and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.1058+1G>A variant is classified as pathogenic.
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV000488992	SCV001334356	pathogenic	not provided	2020-02-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002527026	SCV003551663	pathogenic	Inborn genetic diseases	2020-08-28	criteria provided, single submitter	clinical testing	The alteration is predicted to affect the native donor splice site: The c.1058+1G>A intronic alteration results from a G to A substitution one nucleotide after exon 12 (coding exon 11) of the EFTUD2 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay (Maquat, 2004). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the EFTUD2 c.1058+1G>A alteration was not observed, with coverage at this position. The altered nucleotide is conserved throughout evolution: The c.1058+1G nucleotide is conserved in available vertebrate species. The alteration's predicted effect on splicing: In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, this alteration is classified as pathogenic.