rs56326652
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001852.4(COL9A2):c.738+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,613,950 control chromosomes in the GnomAD database, including 2,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.043 ( 217 hom., cov: 32)
Exomes 𝑓: 0.054 ( 2364 hom. )
Consequence
COL9A2
NM_001852.4 intron
NM_001852.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.267
Genes affected
COL9A2 (HGNC:2218): (collagen type IX alpha 2 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. This chain is unusual in that, unlike the other two type IX alpha chains, it contains a covalently attached glycosaminoglycan side chain. Mutations in this gene are associated with multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 1-40310254-A-G is Benign according to our data. Variant chr1-40310254-A-G is described in ClinVar as [Benign]. Clinvar id is 258394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40310254-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL9A2 | NM_001852.4 | c.738+10T>C | intron_variant | ENST00000372748.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL9A2 | ENST00000372748.8 | c.738+10T>C | intron_variant | 1 | NM_001852.4 | P1 | |||
COL9A2 | ENST00000482722.5 | n.1041+10T>C | intron_variant, non_coding_transcript_variant | 1 | |||||
COL9A2 | ENST00000488463.6 | n.789+10T>C | intron_variant, non_coding_transcript_variant | 5 | |||||
COL9A2 | ENST00000417105.6 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0426 AC: 6481AN: 152114Hom.: 217 Cov.: 32
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GnomAD3 exomes AF: 0.0444 AC: 11170AN: 251408Hom.: 333 AF XY: 0.0458 AC XY: 6221AN XY: 135876
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GnomAD4 exome AF: 0.0544 AC: 79587AN: 1461718Hom.: 2364 Cov.: 34 AF XY: 0.0542 AC XY: 39403AN XY: 727172
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GnomAD4 genome ? AF: 0.0426 AC: 6480AN: 152232Hom.: 217 Cov.: 32 AF XY: 0.0429 AC XY: 3191AN XY: 74424
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Epiphyseal dysplasia, multiple, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Connective tissue disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | May 12, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at