12-47985117-A-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_001844.5(COL2A1):c.1735-24T>C variant causes a intron change. The variant allele was found at a frequency of 0.063 in 1,582,242 control chromosomes in the GnomAD database, including 3,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.051 ( 247 hom., cov: 32)
Exomes 𝑓: 0.064 ( 3405 hom. )
Consequence
COL2A1
NM_001844.5 intron
NM_001844.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.74
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 -18 ACMG points.
BP4
This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 12-47985117-A-G is Benign according to our data. Variant chr12-47985117-A-G is described in ClinVar as [Benign]. Clinvar id is 258216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.1735-24T>C | intron_variant | Intron 26 of 53 | 1 | NM_001844.5 | ENSP00000369889.3 | |||
COL2A1 | ENST00000337299.7 | c.1528-24T>C | intron_variant | Intron 25 of 52 | 1 | ENSP00000338213.6 | ||||
COL2A1 | ENST00000493991.5 | n.659-24T>C | intron_variant | Intron 9 of 36 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0505 AC: 7685AN: 152078Hom.: 247 Cov.: 32
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GnomAD3 exomes AF: 0.0482 AC: 11495AN: 238680Hom.: 394 AF XY: 0.0476 AC XY: 6174AN XY: 129650
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GnomAD4 exome AF: 0.0643 AC: 91991AN: 1430046Hom.: 3405 Cov.: 26 AF XY: 0.0628 AC XY: 44728AN XY: 712670
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GnomAD4 genome AF: 0.0505 AC: 7691AN: 152196Hom.: 247 Cov.: 32 AF XY: 0.0500 AC XY: 3717AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jun 26, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
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not specified Benign:1
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PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
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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