6-33163674-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_080680.3(COL11A2):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,986 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_080680.3 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.*4C>T | 3_prime_UTR_variant | Exon 66 of 66 | ENST00000341947.7 | NP_542411.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947 | c.*4C>T | 3_prime_UTR_variant | Exon 66 of 66 | 5 | NM_080680.3 | ENSP00000339915.2 | |||
COL11A2 | ENST00000374708 | c.*4C>T | 3_prime_UTR_variant | Exon 64 of 64 | 5 | ENSP00000363840.4 | ||||
COL11A2 | ENST00000477772.1 | n.1005C>T | non_coding_transcript_exon_variant | Exon 9 of 9 | 2 | |||||
COL11A2 | ENST00000683572.1 | n.1021C>T | non_coding_transcript_exon_variant | Exon 9 of 9 |
Frequencies
GnomAD3 genomes AF: 0.00181 AC: 275AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00194 AC: 478AN: 245946Hom.: 3 AF XY: 0.00184 AC XY: 247AN XY: 134098
GnomAD4 exome AF: 0.00212 AC: 3090AN: 1460764Hom.: 7 Cov.: 31 AF XY: 0.00209 AC XY: 1521AN XY: 726700
GnomAD4 genome AF: 0.00181 AC: 275AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00193 AC XY: 144AN XY: 74422
ClinVar
Submissions by phenotype
not specified Benign:3
*4C>T in the 3'UTR of COL11A2: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (33/6604) of Finnish chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs186720023). In addition, a number of mammals have a T at the *4 position, including jerboa, mouse, black flying fox, megabat, and brown bat. -
Variant summary: COL11A2 c.*4C>T affects a non-conserved nucleotide located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0021 in 1612986 control chromosomes in the gnomAD database, including 7 homozygotes (gnomAD v4.0.0). The available data on variant occurrences in the general population are insufficient to allow definitive conclusions about variant significance, but do suggest the variant likely represents a benign polymorphism. To our knowledge, no occurrence of c.*4C>T in individuals affected with COL11A2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 178320). Based on the evidence outlined above, the variant was classified as likely benign. -
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Otospondylomegaepiphyseal dysplasia, autosomal dominant Benign:1
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Otospondylomegaepiphyseal dysplasia, autosomal recessive Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:1
See Variant Classification Assertion Criteria. -
Fibrochondrogenesis 2 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Stickler Syndrome, Dominant Benign:1
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Connective tissue disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at