rs727502939
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_080680.3(COL11A2):c.3583-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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).
Frequency
Consequence
NM_080680.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.3583-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.3583-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_080680.3 | P4 | |||
COL11A2 | ENST00000374708.8 | c.3325-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | A1 | ||||
COL11A2 | ENST00000477772.1 | n.273-4287C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000405 AC: 10AN: 246968Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134516
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1460770Hom.: 0 Cov.: 34 AF XY: 0.0000289 AC XY: 21AN XY: 726700
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change falls in intron 48 of the COL11A2 gene. It does not directly change the encoded amino acid sequence of the COL11A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs727502939, gnomAD 0.007%). 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: 162982). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2014 | The 3583-3C>T variant in COL11A2 has not been previously reported in individuals with hearing loss and was absent from large population studies. This variant is located in the 3' splice region. Computational tools do not suggest an impact t o splicing. However, this information is not predictive enough to rule out patho genicity. In summary, the clinical significance of the 3583-3C>T variant is unce rtain. - |
COL11A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 05, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at