rs141140798
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_080680.3(COL11A2):c.1382G>A(p.Gly461Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00039 in 1,611,726 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. G461C) has been classified as Likely benign.
Frequency
Consequence
NM_080680.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.1382G>A | p.Gly461Asp | missense_variant | 13/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.1382G>A | p.Gly461Asp | missense_variant | 13/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.1124G>A | p.Gly375Asp | missense_variant | 11/64 | 5 | A1 | ||
COL11A2 | ENST00000361917.6 | c.11G>A | p.Gly4Asp | missense_variant | 1/24 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000526 AC: 131AN: 249246Hom.: 0 AF XY: 0.000600 AC XY: 81AN XY: 135052
GnomAD4 exome AF: 0.000384 AC: 561AN: 1459412Hom.: 1 Cov.: 33 AF XY: 0.000413 AC XY: 300AN XY: 726184
GnomAD4 genome AF: 0.000440 AC: 67AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | COL11A2: PP3, BS1:Supporting - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 07, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 02, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Gly461Asp var iant in COL11A2 has been previously reported by our laboratory in 2 families wit h hearing loss; however, it did not segregate with hearing loss in one of the fa milies. This variant has been identified in several populations including in 29/ 34412 Latino chromosomes and 87/126550 of European chromosomes by the Genome Ag gregation Consortium (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs14114079 8). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tool s and conservation analyses do not provide strong support for or against an impa ct to the protein. In summary, while the clinical significance of the p.Gly461As p variant is uncertain, the population frequency and non-segregation data sugges t that it is more likely to be benign. ACMG/AMP criteria applied: BS4, BS1_Suppo rting. - |
Hearing impairment Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center | Apr 12, 2021 | PP3_Supporting - |
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