rs774337224
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001379500.1(COL18A1):c.2941G>A(p.Glu981Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000524 in 1,603,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E981G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001379500.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.2941G>A | p.Glu981Lys | missense_variant | 35/42 | ENST00000651438.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL18A1 | ENST00000651438.1 | c.2941G>A | p.Glu981Lys | missense_variant | 35/42 | NM_001379500.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151890Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000542 AC: 12AN: 221364Hom.: 0 AF XY: 0.0000655 AC XY: 8AN XY: 122060
GnomAD4 exome AF: 0.0000503 AC: 73AN: 1451664Hom.: 0 Cov.: 33 AF XY: 0.0000513 AC XY: 37AN XY: 721578
GnomAD4 genome ? AF: 0.0000724 AC: 11AN: 152008Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 978 of the COL18A1 protein (p.Glu978Lys). This variant is present in population databases (rs774337224, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with COL18A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 445666). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 02, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at