1-36097564-G-A

Position:

• chr1-36097564-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005202.4(COL8A2):​c.*5C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,594,428 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (5 hom.)
• Consequence: COL8A2 NM_005202.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-36097564-G-A is Benign according to our data. Variant chr1-36097564-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 282 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A2	NM_005202.4	c.*5C>T		3_prime_UTR_variant	4/4	ENST00000397799.2
COL8A2	NM_001294347.2	c.*5C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL8A2	ENST00000397799.2	c.*5C>T		3_prime_UTR_variant	4/4	5	NM_005202.4	P2
COL8A2	ENST00000481785.1	c.*5C>T		3_prime_UTR_variant	2/2	1		A2
COL8A2	ENST00000303143.9	c.*5C>T		3_prime_UTR_variant	2/2	2		P2

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 282 AN: 151974 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00162 AC: 399 AN: 246100 Hom.: 3 AF XY: 0.00147 AC XY: 196 AN XY: 133424

Gnomad AFR exome AF: 0.000764

Gnomad AMR exome AF: 0.000588

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000665

Gnomad FIN exome AF: 0.000799

Gnomad NFE exome AF: 0.00307

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00253 AC: 3650 AN: 1442338 Hom.: 5 Cov.: 35 AF XY: 0.00239 AC XY: 1714 AN XY: 716040

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.000636

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.000671

Gnomad4 NFE exome AF: 0.00313

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152090 Hom.: 1 Cov.: 33 AF XY: 0.00168 AC XY: 125 AN XY: 74370

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00238 Hom.: 3

Bravo AF: 0.00191

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

COL8A2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.026
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs149180733; hg19: chr1-36563165;