NM_005202.4:c.193+34C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005202.4(COL8A2):c.193+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,595,172 control chromosomes in the GnomAD database, including 442,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32609 hom., cov: 33)

Exomes 𝑓: 0.74 ( 410106 hom. )

Consequence

COL8A2
NM_005202.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.14

Publications

15 publications found

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 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

COL8A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-36100016-G-A is Benign according to our data. Variant chr1-36100016-G-A is described in ClinVar as Benign. ClinVar VariationId is 1255398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 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.193+34C>T		intron	N/A	NP_005193.1
	COL8A2	NM_001294347.2		c.-3+179C>T		intron	N/A	NP_001281276.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL8A2	ENST00000397799.2	TSL:5 MANE Select	c.193+34C>T	intron	N/A	ENSP00000380901.1
COL8A2	ENST00000481785.1	TSL:1	c.-3+179C>T	intron	N/A	ENSP00000436433.1
COL8A2	ENST00000303143.9	TSL:2	c.193+34C>T	intron	N/A	ENSP00000305913.4

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95262

AN:

151990

Hom.:

32600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.654

GnomAD2 exomes

AF:

0.646

AC:

159799

AN:

247318

AF XY:

0.663

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.783

Gnomad OTH exome

AF:

0.702

GnomAD4 exome

AF:

0.743

AC:

1072296

AN:

1443064

Hom.:

410106

Cov.:

AF XY:

0.742

AC XY:

531856

AN XY:

716402

show subpopulations

African (AFR)

AF:

0.378

AC:

12529

AN:

33148

American (AMR)

AF:

0.524

AC:

23334

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

18878

AN:

26020

East Asian (EAS)

AF:

0.224

AC:

8827

AN:

39352

South Asian (SAS)

AF:

0.642

AC:

55147

AN:

85900

European-Finnish (FIN)

AF:

0.685

AC:

36204

AN:

52880

Middle Eastern (MID)

AF:

0.715

AC:

3745

AN:

5236

European-Non Finnish (NFE)

AF:

0.795

AC:

871393

AN:

1096440

Other (OTH)

AF:

0.709

AC:

42239

AN:

59572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

13127

26254

39382

52509

65636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20212

40424

60636

80848

101060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.627

AC:

95315

AN:

152108

Hom.:

32609

Cov.:

AF XY:

0.618

AC XY:

45945

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.394

AC:

16361

AN:

41488

American (AMR)

AF:

0.587

AC:

8965

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

2541

AN:

3470

East Asian (EAS)

AF:

0.236

AC:

1219

AN:

5170

South Asian (SAS)

AF:

0.616

AC:

2973

AN:

4826

European-Finnish (FIN)

AF:

0.670

AC:

7095

AN:

10584

Middle Eastern (MID)

AF:

0.747

AC:

218

AN:

292

European-Non Finnish (NFE)

AF:

0.793

AC:

53881

AN:

67970

Other (OTH)

AF:

0.654

AC:

1382

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1583

3165

4748

6330

7913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.734

Hom.:

164025

Bravo

AF:

0.606

Asia WGS

AF:

0.485

AC:

1690

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Posterior polymorphous corneal dystrophy 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Corneal dystrophy, Fuchs endothelial, 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.35

(source)

DANN

Benign

0.67

PhyloP100

-2.1

PromoterAI

0.00010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over