12-47995235-G-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.762+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,607,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
COL2A1
NM_001844.5 intron
NM_001844.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0180
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=-0.83).
BP6
Variant 12-47995235-G-T is Benign according to our data. Variant chr12-47995235-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 547248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000243 (37/152288) while in subpopulation EAS AF= 0.00193 (10/5186). AF 95% confidence interval is 0.00105. There are 1 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 37 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152170Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 251426Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135890
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GnomAD4 exome AF: 0.0000996 AC: 145AN: 1455584Hom.: 0 Cov.: 29 AF XY: 0.0000856 AC XY: 62AN XY: 724644
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GnomAD4 genome AF: 0.000243 AC: 37AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
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