1-36102635-A-T

Variant names:

• chr1-36102635-A-T
• rs7553155
• NM_005202.4:c.-16-2377T>A

Variant summary

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

The NM_005202.4(COL8A2):​c.-16-2377T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 147,088 control chromosomes in the GnomAD database, including 58,852 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 0.89 (58852 hom., cov: 24)
• Consequence: COL8A2 NM_005202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A2	NM_005202.4	c.-16-2377T>A		intron_variant	Intron 2 of 3	ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2	c.-66-2377T>A		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.-16-2377T>A		intron_variant	Intron 2 of 3	5	NM_005202.4	ENSP00000380901.1

Frequencies

GnomAD3 genomes AF: 0.893 AC: 131323 AN: 146994 Hom.: 58801 Cov.: 24

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.893 AC: 131419 AN: 147088 Hom.: 58852 Cov.: 24 AF XY: 0.893 AC XY: 63566 AN XY: 71202

African (AFR) AF: 0.898 AC: 35658 AN: 39710

American (AMR) AF: 0.924 AC: 13306 AN: 14408

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2995 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5037 AN: 5044

South Asian (SAS) AF: 0.903 AC: 4287 AN: 4750

European-Finnish (FIN) AF: 0.837 AC: 7412 AN: 8856

Middle Eastern (MID) AF: 0.872 AC: 253 AN: 290

European-Non Finnish (NFE) AF: 0.885 AC: 59799 AN: 67594

Other (OTH) AF: 0.890 AC: 1838 AN: 2066

Alfa AF: 0.868 Hom.: 3206

Bravo AF: 0.900

Asia WGS AF: 0.961 AC: 3342 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.79
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7553155; hg19: chr1-36568236;