Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001267723 | SCV001445978 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2020-11-16 | criteria provided, single submitter | curation | The heterozygous p.Glu404Lys variant in CELSR1 was identified by our study in the compound heterozygous state, along with a variant of unknown significance, in 1 individual with suspected Walker-Warburg syndrome. The variant has not been previously reported in individuals with Walker-Warburg syndrome but has been identified in 0.04% (55/126242) of European non-Finnish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs201107590). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Finally, although this gene has been reported in association with Walker-Warburg syndrome, it currently has limited evidence for these associations. In summary, while the clinical significance of the p.Glu404Lys variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BP4 (Richards 2015). |
Ambry Genetics | RCV004035430 | SCV004922605 | uncertain significance | not specified | 2023-12-26 | criteria provided, single submitter | clinical testing | The c.1210G>A (p.E404K) alteration is located in exon 1 (coding exon 1) of the CELSR1 gene. This alteration results from a G to A substitution at nucleotide position 1210, causing the glutamic acid (E) at amino acid position 404 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |