Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pittsburgh Clinical Genomics Laboratory, |
RCV004785099 | SCV005397582 | likely pathogenic | Amelogenesis imperfecta type 1E | 2024-06-26 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (G>A) 1 base downstream of the donor splice site of exon 5 of 7 in the AMELX gene. This variant is absent from ClinVar and has not been observed in individuals affected by an AMELX-related disorder in the published literature, to our knowledge. This variant is absent from the gnomAD v4.1.0 population database (0/~1200000) alleles). Multiple computational tools predict that this variant will cause aberrant splicing by disrupting the exon 5 splice donor site. The nucleotide at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1 |