rs3738360

Variant names:

• chr1-36097557-C-A
• rs3738360
• NM_005202.4:c.*12G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-36097557-C-A
• chr1-36097557-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005202.4(COL8A2):​c.*12G>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 0.862 in 1,584,910 control chromosomes in the GnomAD database, including 601,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (46103 hom., cov: 33)
  • Exomes 𝑓: 0.87 (554961 hom.)
• Consequence: COL8A2 NM_005202.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.631
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-36097557-C-A is Benign according to our data. Variant chr1-36097557-C-A is described in ClinVar as Benign. ClinVar VariationId is 1238973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A2	NM_005202.4	MANE Select	c.*12G>T		3_prime_UTR	Exon 4 of 4	NP_005193.1
	COL8A2	NM_001294347.2		c.*12G>T		3_prime_UTR	Exon 4 of 4	NP_001281276.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A2	ENST00000397799.2	TSL:5 MANE Select	c.*12G>T		3_prime_UTR	Exon 4 of 4	ENSP00000380901.1
	COL8A2	ENST00000481785.1	TSL:1	c.*12G>T		3_prime_UTR	Exon 2 of 2	ENSP00000436433.1
	COL8A2	ENST00000303143.9	TSL:2	c.*12G>T		3_prime_UTR	Exon 2 of 2	ENSP00000305913.4

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115149 AN: 151990 Hom.: 46097 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.776

GnomAD2 exomes AF: 0.795 AC: 193307 AN: 243048 AF XY: 0.815

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.861

Gnomad EAS exome AF: 0.472

Gnomad FIN exome AF: 0.840

Gnomad NFE exome AF: 0.904

Gnomad OTH exome AF: 0.837

GnomAD4 exome AF: 0.873 AC: 1251255 AN: 1432802 Hom.: 554961 Cov.: 28 AF XY: 0.875 AC XY: 622033 AN XY: 710622

African (AFR) AF: 0.495 AC: 16165 AN: 32658

American (AMR) AF: 0.636 AC: 27647 AN: 43438

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 21588 AN: 25208

East Asian (EAS) AF: 0.460 AC: 18077 AN: 39304

South Asian (SAS) AF: 0.865 AC: 73323 AN: 84776

European-Finnish (FIN) AF: 0.845 AC: 43840 AN: 51908

Middle Eastern (MID) AF: 0.855 AC: 4054 AN: 4744

European-Non Finnish (NFE) AF: 0.913 AC: 996876 AN: 1091720

Other (OTH) AF: 0.841 AC: 49685 AN: 59046

GnomAD4 genome AF: 0.757 AC: 115182 AN: 152108 Hom.: 46103 Cov.: 33 AF XY: 0.753 AC XY: 56004 AN XY: 74364

African (AFR) AF: 0.515 AC: 21367 AN: 41474

American (AMR) AF: 0.697 AC: 10668 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2964 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2503 AN: 5148

South Asian (SAS) AF: 0.855 AC: 4120 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8910 AN: 10604

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61886 AN: 67978

Other (OTH) AF: 0.779 AC: 1644 AN: 2110

Alfa AF: 0.832 Hom.: 6700

Bravo AF: 0.729

Asia WGS AF: 0.707 AC: 2457 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Corneal dystrophy, Fuchs endothelial, 1 (1)
-	-	1	Posterior polymorphous corneal dystrophy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.63
Mutation Taster		=97/3	polymorphism

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: rs3738360; hg19: chr1-36563158; COSMIC: COSV57442863; COSMIC: COSV57442863;