2-26402066-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_145038.5(DRC1):āc.77C>Gā(p.Ser26Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,368 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 Uncertain significance (ā ).
Frequency
Consequence
NM_145038.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DRC1 | ENST00000288710.7 | c.77C>G | p.Ser26Trp | missense_variant | Exon 1 of 17 | 2 | NM_145038.5 | ENSP00000288710.2 | ||
DRC1 | ENST00000421869.5 | n.77C>G | non_coding_transcript_exon_variant | Exon 1 of 8 | 1 | ENSP00000414375.1 | ||||
DRC1 | ENST00000649059.1 | n.62C>G | non_coding_transcript_exon_variant | Exon 1 of 16 | ENSP00000497543.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461046Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726822
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74482
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
This sequence change replaces serine with tryptophan at codon 26 of the DRC1 protein (p.Ser26Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DRC1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at