chr12-47996652-A-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001844.5(COL2A1):c.532-27T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,601,660 control chromosomes in the GnomAD database, including 1,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 55 hom., cov: 33)
Exomes 𝑓: 0.034 ( 980 hom. )
Consequence
COL2A1
NM_001844.5 intron
NM_001844.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.407
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 12-47996652-A-T is Benign according to our data. Variant chr12-47996652-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 258241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3555/152308) while in subpopulation NFE AF= 0.0348 (2365/68034). AF 95% confidence interval is 0.0336. There are 55 homozygotes in gnomad4. There are 1712 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 3555 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL2A1 | NM_001844.5 | c.532-27T>A | intron_variant | ENST00000380518.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.532-27T>A | intron_variant | 1 | NM_001844.5 | P1 | |||
COL2A1 | ENST00000337299.7 | c.325-27T>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0234 AC: 3554AN: 152190Hom.: 55 Cov.: 33
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GnomAD3 exomes AF: 0.0243 AC: 6104AN: 251146Hom.: 116 AF XY: 0.0243 AC XY: 3292AN XY: 135700
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GnomAD4 exome AF: 0.0338 AC: 48962AN: 1449352Hom.: 980 Cov.: 28 AF XY: 0.0326 AC XY: 23521AN XY: 721882
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GnomAD4 genome AF: 0.0233 AC: 3555AN: 152308Hom.: 55 Cov.: 33 AF XY: 0.0230 AC XY: 1712AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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