rs80358192

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_005202.4(COL8A2):c.1349T>G(p.Leu450Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

COL8A2
NM_005202.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 0.879

Publications

62 publications found

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 Gene-Disease associations (from GenCC):

corneal dystrophy, Fuchs endothelial, 1
Inheritance: AD Classification: STRONG Submitted by: G2P
posterior polymorphous corneal dystrophy 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Fuchs' endothelial dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL8A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-36098332-A-C is Pathogenic according to our data. Variant chr1-36098332-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 17148.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4 link	c.1349T>G	p.Leu450Trp	missense_variant	Exon 4 of 4	ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2 link	c.1154T>G	p.Leu385Trp	missense_variant	Exon 4 of 4		NP_001281276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
COL8A2	ENST00000397799.2 link	c.1349T>G	p.Leu450Trp	missense_variant	Exon 4 of 4	5	NM_005202.4	ENSP00000380901.1
COL8A2	ENST00000481785.1 link	c.1154T>G	p.Leu385Trp	missense_variant	Exon 2 of 2	1		ENSP00000436433.1
COL8A2	ENST00000303143.9 link	c.1349T>G	p.Leu450Trp	missense_variant	Exon 2 of 2	2		ENSP00000305913.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

151672

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000286

AC:

AN:

1398282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31602

American (AMR)

AF:

0.00

AC:

AN:

36228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35840

South Asian (SAS)

AF:

0.00

AC:

AN:

79328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4622

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1079660

Other (OTH)

AF:

0.00

AC:

AN:

57882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Posterior polymorphous corneal dystrophy 2

Pathogenic:1

Mar 28, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Corneal dystrophy, Fuchs endothelial, 1

Pathogenic:1

Mar 28, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.090

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.30

T;T;.

Eigen

Benign

0.027

Eigen_PC

Benign

0.000047

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.0

.;T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Uncertain

0.085

MutationAssessor

Benign

2.0

M;M;.

PhyloP100

0.88

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.63

Sift

Uncertain

0.028

D;D;T

Sift4G

Uncertain

0.018

D;D;D

Vest4

0.34

ClinPred

0.20

GERP RS

4.4

Varity_R

0.090

gMVP

0.47

Mutation Taster

=15/85

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over