1-36097555-A-AC

Position:

• chr1-36097555-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005202.4(COL8A2):​c.*13_*14insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,573,498 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (10 hom.)
• Consequence: COL8A2 NM_005202.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.763

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.

• BP6: Variant 1-36097555-A-AC is Benign according to our data. Variant chr1-36097555-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 1328777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (995/151570) while in subpopulation AFR AF= 0.0205 (843/41096). AF 95% confidence interval is 0.0194. There are 7 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 995 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A2	NM_005202.4	c.*13_*14insG		3_prime_UTR_variant	4/4	ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2	c.*13_*14insG		3_prime_UTR_variant	4/4		NP_001281276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL8A2	ENST00000397799.2	c.*13_*14insG		3_prime_UTR_variant	4/4	5	NM_005202.4	ENSP00000380901	P2
COL8A2	ENST00000481785.1	c.*13_*14insG		3_prime_UTR_variant	2/2	1		ENSP00000436433	A2
COL8A2	ENST00000303143.9	c.*13_*14insG		3_prime_UTR_variant	2/2	2		ENSP00000305913	P2

Frequencies

GnomAD3 genomes AF: 0.00656 AC: 993 AN: 151454 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00303

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00428

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00432

GnomAD3 exomes AF: 0.00283 AC: 681 AN: 240424 Hom.: 3 AF XY: 0.00265 AC XY: 346 AN XY: 130484

Gnomad AFR exome AF: 0.0201

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00844

Gnomad EAS exome AF: 0.00316

Gnomad SAS exome AF: 0.00421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00126 AC: 1787 AN: 1421928 Hom.: 10 Cov.: 25 AF XY: 0.00124 AC XY: 874 AN XY: 706034

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.00894

Gnomad4 EAS exome AF: 0.00181

Gnomad4 SAS exome AF: 0.00397

Gnomad4 FIN exome AF: 0.0000579

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00656 AC: 995 AN: 151570 Hom.: 7 Cov.: 33 AF XY: 0.00629 AC XY: 466 AN XY: 74088

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.00302

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00429

Gnomad4 SAS AF: 0.00396

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00427

Asia WGS AF: 0.00462 AC: 16 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs201628588; hg19: chr1-36563156;