rs96067

Variant names:

• chr1-36106319-G-A
• rs96067
• NM_005202.4:c.-16-6061C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-36106319-G-A
• chr1-36106319-G-C
• chr1-36106319-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005202.4(COL8A2):​c.-16-6061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,450 control chromosomes in the GnomAD database, including 40,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40393 hom., cov: 28)
• Consequence: COL8A2 NM_005202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 30 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4	c.-16-6061C>T		intron_variant	Intron 2 of 3	ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2	c.-66-6061C>T		intron_variant	Intron 2 of 3		NP_001281276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL8A2	ENST00000397799.2	c.-16-6061C>T		intron_variant	Intron 2 of 3	5	NM_005202.4	ENSP00000380901.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109539 AN: 151344 Hom.: 40365 Cov.: 28

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 109619 AN: 151450 Hom.: 40393 Cov.: 28 AF XY: 0.716 AC XY: 52933 AN XY: 73944

African (AFR) AF: 0.646 AC: 26622 AN: 41230

American (AMR) AF: 0.654 AC: 9952 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2630 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2458 AN: 5118

South Asian (SAS) AF: 0.647 AC: 3109 AN: 4808

European-Finnish (FIN) AF: 0.738 AC: 7710 AN: 10442

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.806 AC: 54704 AN: 67862

Other (OTH) AF: 0.727 AC: 1523 AN: 2096

Alfa AF: 0.775 Hom.: 190561

Bravo AF: 0.712

Asia WGS AF: 0.603 AC: 2097 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.47
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs96067; hg19: chr1-36571920;