1-36097720-C-T
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2
The NM_005202.4(COL8A2):c.1961G>A(p.Gly654Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005202.4 missense
Scores
Clinical Significance
Conservation
Publications
- corneal dystrophy, Fuchs endothelial, 1Inheritance: AD Classification: STRONG Submitted by: G2P
- posterior polymorphous corneal dystrophy 2Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Fuchs' endothelial dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- posterior polymorphous corneal dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL8A2 | ENST00000397799.2 | c.1961G>A | p.Gly654Asp | missense_variant | Exon 4 of 4 | 5 | NM_005202.4 | ENSP00000380901.1 | ||
COL8A2 | ENST00000481785.1 | c.1766G>A | p.Gly589Asp | missense_variant | Exon 2 of 2 | 1 | ENSP00000436433.1 | |||
COL8A2 | ENST00000303143.9 | c.1961G>A | p.Gly654Asp | missense_variant | Exon 2 of 2 | 2 | ENSP00000305913.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000279 AC: 7AN: 251238 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461414Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4AN XY: 727020 show subpopulations
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74328 show subpopulations
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1961G>A (p.G654D) alteration is located in exon 2 (coding exon 2) of the COL8A2 gene. This alteration results from a G to A substitution at nucleotide position 1961, causing the glycine (G) at amino acid position 654 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at