rs274754
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005202.4(COL8A2):c.193+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,595,172 control chromosomes in the GnomAD database, including 442,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.63 ( 32609 hom., cov: 33)
Exomes 𝑓: 0.74 ( 410106 hom. )
Consequence
COL8A2
NM_005202.4 intron
NM_005202.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.14
Genes affected
COL8A2 (HGNC:2216): (collagen type VIII alpha 2 chain) This gene encodes the alpha 2 chain of type VIII collagen. This protein is a major component of the basement membrane of the corneal endothelium and forms homo- or heterotrimers with alpha 1 (VIII) type collagens. Defects in this gene are associated with Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
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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=-0.86).
BP6
?
Variant 1-36100016-G-A is Benign according to our data. Variant chr1-36100016-G-A is described in ClinVar as [Benign]. Clinvar id is 1255398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL8A2 | NM_005202.4 | c.193+34C>T | intron_variant | ENST00000397799.2 | |||
COL8A2 | NM_001294347.2 | c.-3+179C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL8A2 | ENST00000397799.2 | c.193+34C>T | intron_variant | 5 | NM_005202.4 | P2 | |||
COL8A2 | ENST00000481785.1 | c.-3+179C>T | intron_variant | 1 | A2 | ||||
COL8A2 | ENST00000303143.9 | c.193+34C>T | intron_variant | 2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.627 AC: 95262AN: 151990Hom.: 32600 Cov.: 33
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GnomAD3 exomes AF: 0.646 AC: 159799AN: 247318Hom.: 55581 AF XY: 0.663 AC XY: 88969AN XY: 134176
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GnomAD4 exome AF: 0.743 AC: 1072296AN: 1443064Hom.: 410106 Cov.: 30 AF XY: 0.742 AC XY: 531856AN XY: 716402
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GnomAD4 genome ? AF: 0.627 AC: 95315AN: 152108Hom.: 32609 Cov.: 33 AF XY: 0.618 AC XY: 45945AN XY: 74370
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Posterior polymorphous corneal dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Corneal dystrophy, Fuchs endothelial, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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Name
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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