rs141321284
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001844.5(COL2A1):c.1635C>T(p.Asn545=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
COL2A1
NM_001844.5 synonymous
NM_001844.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.48
Genes affected
COL2A1 (HGNC:2200): (collagen type II alpha 1 chain) This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 12-47985773-G-A is Benign according to our data. Variant chr12-47985773-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.48 with no splicing effect.
BS2
?
High AC in GnomAd4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL2A1 | NM_001844.5 | c.1635C>T | p.Asn545= | synonymous_variant | 25/54 | ENST00000380518.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.1635C>T | p.Asn545= | synonymous_variant | 25/54 | 1 | NM_001844.5 | P1 | |
COL2A1 | ENST00000337299.7 | c.1428C>T | p.Asn476= | synonymous_variant | 24/53 | 1 | |||
COL2A1 | ENST00000493991.5 | n.559C>T | non_coding_transcript_exon_variant | 8/37 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000802 AC: 20AN: 249234Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 134868
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GnomAD4 exome AF: 0.000116 AC: 169AN: 1461444Hom.: 0 Cov.: 34 AF XY: 0.000125 AC XY: 91AN XY: 727000
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 15, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 11, 2023 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 18, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at