rs145541630
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP2
The NM_000089.4(COL1A2):c.3368G>A(p.Arg1123His) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1123C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000089.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A2 | NM_000089.4 | c.3368G>A | p.Arg1123His | missense_variant | 49/52 | ENST00000297268.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A2 | ENST00000297268.11 | c.3368G>A | p.Arg1123His | missense_variant | 49/52 | 1 | NM_000089.4 | P1 | |
COL1A2 | ENST00000464916.1 | n.416G>A | non_coding_transcript_exon_variant | 1/4 | 2 | ||||
COL1A2 | ENST00000481570.5 | n.4149G>A | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251154Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135726
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727236
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Stenson et al., 2014); Has not been previously published as pathogenic or benign to our knowledge - |
Osteogenesis imperfecta type I;C0268335:Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL1A2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 665717). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs145541630, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1123 of the COL1A2 protein (p.Arg1123His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at