1-36097826-C-T
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005202.4(COL8A2):c.1855G>A(p.Val619Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL8A2 | ENST00000397799.2 | c.1855G>A | p.Val619Ile | missense_variant | Exon 4 of 4 | 5 | NM_005202.4 | ENSP00000380901.1 | ||
COL8A2 | ENST00000481785.1 | c.1660G>A | p.Val554Ile | missense_variant | Exon 2 of 2 | 1 | ENSP00000436433.1 | |||
COL8A2 | ENST00000303143.9 | c.1855G>A | p.Val619Ile | missense_variant | Exon 2 of 2 | 2 | ENSP00000305913.4 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152246Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000717 AC: 18AN: 250988 AF XY: 0.0000589 show subpopulations
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461128Hom.: 0 Cov.: 37 AF XY: 0.0000248 AC XY: 18AN XY: 726894 show subpopulations
GnomAD4 genome AF: 0.000158 AC: 24AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74374 show subpopulations
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1855G>A (p.V619I) 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 1855, causing the valine (V) at amino acid position 619 to be replaced by an isoleucine (I). 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