rs727504229

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_005202.4(COL8A2):​c.1363_1364delinsGT​(p.Gln455Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

COL8A2
NM_005202.4 missense

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.82
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-36098317-TG-AC is Pathogenic according to our data. Variant chr1-36098317-TG-AC is described in ClinVar as [Pathogenic]. Clinvar id is 167868.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL8A2NM_005202.4 linkuse as main transcriptc.1363_1364delinsGT p.Gln455Val missense_variant 4/4 ENST00000397799.2 NP_005193.1
COL8A2NM_001294347.2 linkuse as main transcriptc.1168_1169delinsGT p.Gln390Val missense_variant 4/4 NP_001281276.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL8A2ENST00000397799.2 linkuse as main transcriptc.1363_1364delinsGT p.Gln455Val missense_variant 4/45 NM_005202.4 ENSP00000380901 P2
COL8A2ENST00000481785.1 linkuse as main transcriptc.1168_1169delinsGT p.Gln390Val missense_variant 2/21 ENSP00000436433 A2
COL8A2ENST00000303143.9 linkuse as main transcriptc.1363_1364delinsGT p.Gln455Val missense_variant 2/22 ENSP00000305913 P2

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Corneal dystrophy, Fuchs endothelial, 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs727504229; hg19: chr1-36563918; API