Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002444419 | SCV002682925 | uncertain significance | Primary ciliary dyskinesia | 2019-09-17 | criteria provided, single submitter | clinical testing | The p.L426* variant (also known as c.1277T>A), located in coding exon 13 of the NME8 gene, results from a T to A substitution at nucleotide position 1277. This changes the amino acid from a leucine to a stop codon within coding exon 13. This alteration was reported in a 13 year old girl with a clinical diagnosis of PCD and electron microscopy results showing that 66% of her respiratory cilia had shortened or absent outer dynein arms; a second disease-causing allele was not detected (Duriez B et al. Proc. Natl. Acad. Sci. U.S.A., 2007 Feb;104:3336-41). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of NME8 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Preventiongenetics, |
RCV003415635 | SCV004115497 | likely pathogenic | NME8-related condition | 2023-03-03 | criteria provided, single submitter | clinical testing | The NME8 c.1277T>A variant is predicted to result in premature protein termination (p.Leu426*). This variant has been reported in a patient with autosomal recessive primary ciliary dyskinesia (Duriez et al. 2007. PubMed ID: 17360648). This variant is reported in 0.043% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-37927908-T-A). Nonsense variants in NME8 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
Invitae | RCV000003412 | SCV004278333 | uncertain significance | Primary ciliary dyskinesia 6 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu426*) in the NME8 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NME8 cause disease. This variant is present in population databases (rs121918300, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with NME8-related conditions. ClinVar contains an entry for this variant (Variation ID: 3256). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000003412 | SCV000023570 | pathogenic | Primary ciliary dyskinesia 6 | 2007-02-27 | no assertion criteria provided | literature only | |
Gene |
RCV000003412 | SCV000086969 | not provided | Primary ciliary dyskinesia 6 | no assertion provided | literature only |