rs727504458
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The NM_080680.3(COL11A2):c.4705C>T(p.Arg1569Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1569H) has been classified as Uncertain significance.
Frequency
Consequence
NM_080680.3 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 |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.4705C>T | p.Arg1569Cys | missense_variant | 63/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.4705C>T | p.Arg1569Cys | missense_variant | 63/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.4447C>T | p.Arg1483Cys | missense_variant | 61/64 | 5 | A1 | ||
COL11A2 | ENST00000477772.1 | n.495C>T | non_coding_transcript_exon_variant | 6/9 | 2 | ||||
COL11A2 | ENST00000683572.1 | n.511C>T | non_coding_transcript_exon_variant | 6/9 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152088Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135302
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461238Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 726964
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152088Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); 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 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 05, 2013 | The Arg1569Cys variant in COL11A2 has not been reported in affected individuals or in large population studies. Computational analyses (biochemical amino acid p roperties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg156 9Cys variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | The c.4705C>T (p.R1569C) alteration is located in exon 63 (coding exon 63) of the COL11A2 gene. This alteration results from a C to T substitution at nucleotide position 4705, causing the arginine (R) at amino acid position 1569 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at