Variant chr1-36097872-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005202.4(COL8A2):c.1809C>G(p.Ser603Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,374 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. Synonymous variant affecting the same amino acid position (i.e. S603S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL8A2
NM_005202.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.986

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23047575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4 link	c.1809C>G	p.Ser603Arg	missense_variant	Exon 4 of 4	ENST00000397799.2	NP_005193.1	P25067
COL8A2	NM_001294347.2 link	c.1614C>G	p.Ser538Arg	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.1809C>G	p.Ser603Arg	missense_variant	Exon 4 of 4	5	NM_005202.4	ENSP00000380901.1	P25067
COL8A2	ENST00000481785.1 link	c.1614C>G	p.Ser538Arg	missense_variant	Exon 2 of 2	1		ENSP00000436433.1	E9PP49
COL8A2	ENST00000303143.9 link	c.1809C>G	p.Ser603Arg	missense_variant	Exon 2 of 2	2		ENSP00000305913.4	P25067

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.42

N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.2

N;N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.066

T;T;T

Polyphen

0.65

P;P;.

Vest4

0.34

MutPred

0.58

Loss of glycosylation at S603 (P = 0.0204);Loss of glycosylation at S603 (P = 0.0204);.;

MVP

0.50

MPC

1.0

ClinPred

0.86

GERP RS

-2.7

Varity_R

0.38

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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