Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002362568 | SCV002666596 | pathogenic | Primary ciliary dyskinesia | 2021-06-21 | criteria provided, single submitter | clinical testing | The p.Y4121* variant (also known as c.12363C>G), located in coding exon 75 of the DNAH11 gene, results from a C to G substitution at nucleotide position 12363. This changes the amino acid from a tyrosine to a stop codon within coding exon 75. In one family, this variant has been detected in trans with another variant in DNAH11, and both segregate with primary ciliary dyskinesia (PCD) in affected family members (Schwabe GC et al. Hum Mutat, 2008 Feb;29:289-98). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV002362568 | SCV004400344 | pathogenic | Primary ciliary dyskinesia | 2023-09-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6475). This variant is also known as p.Y4128X. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 18022865). This variant is present in population databases (rs121908855, gnomAD 0.05%). This sequence change creates a premature translational stop signal (p.Tyr4121*) in the DNAH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). |
OMIM | RCV000006848 | SCV000027044 | pathogenic | Primary ciliary dyskinesia 7 | 2008-02-01 | no assertion criteria provided | literature only |