Variant rs141682102 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005202.4(COL8A2):c.2003G>T(p.Arg668Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R668Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL8A2
NM_005202.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

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]

COL8A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33193308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4 link	c.2003G>T	p.Arg668Leu	missense_variant	Exon 4 of 4	ENST00000397799.2	NP_005193.1	P25067
COL8A2	NM_001294347.2 link	c.1808G>T	p.Arg603Leu	missense_variant	Exon 4 of 4		NP_001281276.1	P25067E9PP49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL8A2	ENST00000397799.2 link	c.2003G>T	p.Arg668Leu	missense_variant	Exon 4 of 4	5	NM_005202.4	ENSP00000380901.1	P25067
COL8A2	ENST00000481785.1 link	c.1808G>T	p.Arg603Leu	missense_variant	Exon 2 of 2	1		ENSP00000436433.1	E9PP49
COL8A2	ENST00000303143.9 link	c.2003G>T	p.Arg668Leu	missense_variant	Exon 2 of 2	2		ENSP00000305913.4	P25067

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251154

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.0020

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.5

L;L;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.28

B;B;.

Vest4

0.38

MutPred

0.56

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.69

MPC

0.86

ClinPred

0.82

GERP RS

3.2

Varity_R

0.14

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over