rs72657393
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001277115.2(DNAH11):c.10324C>T(p.Gln3442Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,534,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q3442Q) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001277115.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.10324C>T | p.Gln3442Ter | stop_gained | 63/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.10324C>T | p.Gln3442Ter | stop_gained | 63/82 | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000145 AC: 2AN: 1382258Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 677952
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | This sequence change creates a premature translational stop signal (p.Gln3442*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 22184204). ClinVar contains an entry for this variant (Variation ID: 238887). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The p.Q3442* pathogenic mutation (also known as c.10324C>T), located in coding exon 63 of the DNAH11 gene, results from a C to T substitution at nucleotide position 10324. This changes the amino acid from a glutamine to a stop codon within coding exon 63. This alteration has been reported in a primary ciliary dyskinesia cohort (Knowles MR et al. Thorax, 2012 May;67:433-41). In addition, this variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at