Genetic Variant COL8A2:c.*13delG (chr1-36097555-AC-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005202.4(COL8A2):c.*13delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,573,498 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

COL8A2
NM_005202.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4 link	c.*13delG		3_prime_UTR_variant	Exon 4 of 4	ENST00000397799.2	NP_005193.1	P25067
COL8A2	NM_001294347.2 link	c.*13delG		3_prime_UTR_variant	Exon 4 of 4		NP_001281276.1	P25067E9PP49

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL8A2	ENST00000397799.2 link	c.*13delG	3_prime_UTR_variant	Exon 4 of 4	5	NM_005202.4	ENSP00000380901.1	P25067
COL8A2	ENST00000481785.1 link	c.*13delG	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000436433.1	E9PP49
COL8A2	ENST00000303143.9 link	c.*13delG	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000305913.4	P25067

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

240424

AF XY:

0.00000766

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000915

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000914

AC:

AN:

1421924

Hom.:

Cov.:

AF XY:

0.00000850

AC XY:

AN XY:

706024

show subpopulations

African (AFR)

AF:

0.0000309

AC:

AN:

32390

American (AMR)

AF:

0.0000230

AC:

AN:

43392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39276

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4748

European-Non Finnish (NFE)

AF:

0.00000647

AC:

AN:

1082008

Other (OTH)

AF:

0.0000170

AC:

AN:

58666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151574

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

41098

American (AMR)

AF:

0.000131

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.76

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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1-36097555-AC-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over