Variant chr1-36097557-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.631

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1238973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-36097557-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A2	NM_005202.4 linkuse as main transcript	c.*12G>T		3_prime_UTR_variant	4/4	ENST00000397799.2
COL8A2	NM_001294347.2 linkuse as main transcript	c.*12G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
COL8A2	ENST00000397799.2 linkuse as main transcript	c.*12G>T	3_prime_UTR_variant	4/4	5	NM_005202.4	P2
COL8A2	ENST00000481785.1 linkuse as main transcript	c.*12G>T	3_prime_UTR_variant	2/2	1		A2
COL8A2	ENST00000303143.9 linkuse as main transcript	c.*12G>T	3_prime_UTR_variant	2/2	2		P2

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115149

AN:

151990

Hom.:

46097

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.795

AC:

193307

AN:

243048

Hom.:

79949

AF XY:

0.815

AC XY:

107399

AN XY:

131824

show subpopulations

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 SAS exome

AF:

0.869

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.:

AF XY:

0.875

AC XY:

622033

AN XY:

710622

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.856

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.865

Gnomad4 FIN exome

AF:

0.845

Gnomad4 NFE exome

AF:

0.913

Gnomad4 OTH exome

AF:

0.841

GnomAD4 genome

AF:

0.757

AC:

115182

AN:

152108

Hom.:

46103

Cov.:

AF XY:

0.753

AC XY:

56004

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.697

Gnomad4 ASJ

AF:

0.854

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.855

Gnomad4 FIN

AF:

0.840

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.779

Alfa

AF:

0.832

Hom.:

6700

Bravo

AF:

0.729

Asia WGS

AF:

0.707

AC:

2457

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Posterior polymorphous corneal dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Corneal dystrophy, Fuchs endothelial, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over