1-36101742-A-G

Variant names:

• chr1-36101742-A-G
• rs7550047
• NM_005202.4:c.-16-1484T>C

Variant summary

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

The NM_005202.4(COL8A2):​c.-16-1484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,268 control chromosomes in the GnomAD database, including 1,907 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 0.14 (1907 hom., cov: 32)
• Consequence: COL8A2 NM_005202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005202.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A2	NM_005202.4	MANE Select	c.-16-1484T>C		intron	N/A	NP_005193.1	P25067
	COL8A2	NM_001294347.2		c.-66-1484T>C		intron	N/A	NP_001281276.1	E9PP49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A2	ENST00000397799.2	TSL:5 MANE Select	c.-16-1484T>C		intron	N/A	ENSP00000380901.1	P25067

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21185 AN: 152150 Hom.: 1904 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.139 AC: 21198 AN: 152268 Hom.: 1907 Cov.: 32 AF XY: 0.141 AC XY: 10516 AN XY: 74460

African (AFR) AF: 0.247 AC: 10260 AN: 41520

American (AMR) AF: 0.111 AC: 1694 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1138 AN: 5188

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4828

European-Finnish (FIN) AF: 0.0822 AC: 872 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5422 AN: 68038

Other (OTH) AF: 0.117 AC: 246 AN: 2110

Alfa AF: 0.0885 Hom.: 627

Bravo AF: 0.144

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.47
PhyloP100		1.6
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: rs7550047; hg19: chr1-36567343;