Variant chr1-36097871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005202.4(COL8A2):c.1810G>A(p.Gly604Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

COL8A2
NM_005202.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27648512).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A2	NM_005202.4 linkuse as main transcript	c.1810G>A	p.Gly604Ser	missense_variant	4/4	ENST00000397799.2
COL8A2	NM_001294347.2 linkuse as main transcript	c.1615G>A	p.Gly539Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL8A2	ENST00000397799.2 linkuse as main transcript	c.1810G>A	p.Gly604Ser	missense_variant	4/4	5	NM_005202.4	P2
COL8A2	ENST00000481785.1 linkuse as main transcript	c.1615G>A	p.Gly539Ser	missense_variant	2/2	1		A2
COL8A2	ENST00000303143.9 linkuse as main transcript	c.1810G>A	p.Gly604Ser	missense_variant	2/2	2		P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249750

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000616

AC:

AN:

1460386

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.1810G>A (p.G604S) 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 1810, causing the glycine (G) at amino acid position 604 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Benign

0.67

N;N;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.95

P;P;.

Vest4

0.19

MutPred

0.51

Loss of glycosylation at S603 (P = 0.0368);Loss of glycosylation at S603 (P = 0.0368);.;

MVP

0.63

MPC

0.58

ClinPred

0.66

GERP RS

3.6

Varity_R

0.17

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over