Variant 1-36100016-G-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.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

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=-0.86).

BP6

Variant 1-36100016-G-A is Benign according to our data. Variant chr1-36100016-G-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A2	NM_005202.4 linkuse as main transcript	c.193+34C>T		intron_variant		ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2 linkuse as main transcript	c.-3+179C>T		intron_variant			NP_001281276.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
COL8A2	ENST00000397799.2 linkuse as main transcript	c.193+34C>T	intron_variant	5	NM_005202.4	ENSP00000380901	P2
COL8A2	ENST00000481785.1 linkuse as main transcript	c.-3+179C>T	intron_variant	1		ENSP00000436433	A2
COL8A2	ENST00000303143.9 linkuse as main transcript	c.193+34C>T	intron_variant	2		ENSP00000305913	P2

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

GnomAD3 exomes

AF:

0.646

AC:

159799

AN:

247318

Hom.:

55581

AF XY:

0.663

AC XY:

88969

AN XY:

134176

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 SAS exome

AF:

0.640

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

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.726

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.685

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.709

GnomAD4 genome

AF:

0.627

AC:

95315

AN:

152108

Hom.:

32609

Cov.:

AF XY:

0.618

AC XY:

45945

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.587

Gnomad4 ASJ

AF:

0.732

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.793

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.755

Hom.:

74319

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Posterior polymorphous corneal dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

-0.86

CADD

Benign

0.35

DANN

Benign

0.67

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