17-44902645-CAGAG-C
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_213607.3(CCDC103):c.566_569delAGAG(p.Glu189AlafsTer18) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000229 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_213607.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC103 | ENST00000417826.3 | c.566_569delAGAG | p.Glu189AlafsTer18 | frameshift_variant | Exon 4 of 4 | 1 | NM_213607.3 | ENSP00000391692.2 | ||
CCDC103 | ENST00000410006.6 | c.566_569delAGAG | p.Glu189AlafsTer18 | frameshift_variant | Exon 4 of 4 | 2 | ENSP00000387252.1 | |||
CCDC103 | ENST00000357776.6 | c.566_569delAGAG | p.Glu189AlafsTer18 | frameshift_variant | Exon 4 of 4 | 2 | ENSP00000350420.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152016Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249972Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135204
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461832Hom.: 0 AF XY: 0.0000275 AC XY: 20AN XY: 727224
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74240
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CCDC103 protein in which other variant(s) (p.Ser190Argfs*19) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (Invitae). This variant is present in population databases (rs746242380, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Glu189Alafs*18) in the CCDC103 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the CCDC103 protein. -
Primary ciliary dyskinesia 17 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at