rs147328015
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP6
The NM_080680.3(COL11A2):c.1817C>T(p.Ser606Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000031 in 1,612,512 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. S606W) has been classified as Uncertain significance.
Frequency
Consequence
NM_080680.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.1817C>T | p.Ser606Leu | missense_variant, splice_region_variant | 20/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.1817C>T | p.Ser606Leu | missense_variant, splice_region_variant | 20/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.1559C>T | p.Ser520Leu | missense_variant, splice_region_variant | 18/64 | 5 | A1 | ||
COL11A2 | ENST00000361917.6 | c.446C>T | p.Ser149Leu | missense_variant, splice_region_variant | 8/24 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000528 AC: 8AN: 151614Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000365 AC: 9AN: 246588Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134400
GnomAD4 exome AF: 0.0000288 AC: 42AN: 1460780Hom.: 0 Cov.: 35 AF XY: 0.0000358 AC XY: 26AN XY: 726706
GnomAD4 genome AF: 0.0000527 AC: 8AN: 151732Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3AN XY: 74152
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 606 of the COL11A2 protein (p.Ser606Leu). This variant is present in population databases (rs147328015, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with COL11A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 547217). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | GeneDx | Jan 03, 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; This variant is associated with the following publications: (PMID: 27535533) - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at