Variant 1-36097923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005202.4(COL8A2):c.1758C>T(p.Pro586=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,611,396 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 43 hom., cov: 33)

Exomes 𝑓: 0.024 ( 509 hom. )

Consequence

COL8A2
NM_005202.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.67

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-36097923-G-A is Benign according to our data. Variant chr1-36097923-G-A is described in ClinVar as [Benign]. Clinvar id is 1258933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0177 (2691/152340) while in subpopulation SAS AF= 0.03 (145/4834). AF 95% confidence interval is 0.026. There are 43 homozygotes in gnomad4. There are 1279 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2691 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A2	NM_005202.4 linkuse as main transcript	c.1758C>T	p.Pro586=	synonymous_variant	4/4	ENST00000397799.2	NP_005193.1
COL8A2	NM_001294347.2 linkuse as main transcript	c.1563C>T	p.Pro521=	synonymous_variant	4/4		NP_001281276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
COL8A2	ENST00000397799.2 linkuse as main transcript	c.1758C>T	p.Pro586=	synonymous_variant	4/4	5	NM_005202.4	ENSP00000380901	P2
COL8A2	ENST00000481785.1 linkuse as main transcript	c.1563C>T	p.Pro521=	synonymous_variant	2/2	1		ENSP00000436433	A2
COL8A2	ENST00000303143.9 linkuse as main transcript	c.1758C>T	p.Pro586=	synonymous_variant	2/2	2		ENSP00000305913	P2

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2691

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0211

AC:

5225

AN:

247290

Hom.:

AF XY:

0.0226

AC XY:

3036

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.00361

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0637

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.0322

Gnomad FIN exome

AF:

0.00969

Gnomad NFE exome

AF:

0.0251

Gnomad OTH exome

AF:

0.0188

GnomAD4 exome

AF:

0.0237

AC:

34562

AN:

1459056

Hom.:

509

Cov.:

AF XY:

0.0242

AC XY:

17594

AN XY:

725946

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0677

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0322

Gnomad4 FIN exome

AF:

0.00867

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0177

AC:

2691

AN:

152340

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1279

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00447

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.00828

Gnomad4 NFE

AF:

0.0257

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 27, 2020	This variant is associated with the following publications: (PMID: 25007886) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.053

DANN

Benign

0.90

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