Variant rs12693526 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_000393.5(COL5A2):c.4113+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,432,150 control chromosomes in the GnomAD database, including 438,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39695 hom., cov: 32)

Exomes 𝑓: 0.79 ( 398496 hom. )

Consequence

COL5A2
NM_000393.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.271

Variant links:

Genes affected

COL5A2 (HGNC:2210): (collagen type V alpha 2 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]

COL5A2 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 2-189036569-G-A is Benign according to our data. Variant chr2-189036569-G-A is described in ClinVar as [Benign]. Clinvar id is 256004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COL5A2	NM_000393.5 linkuse as main transcript	c.4113+47C>T	intron_variant	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4 linkuse as main transcript	c.3975+47C>T	intron_variant		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.3975+47C>T	intron_variant		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.3975+47C>T	intron_variant		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9 linkuse as main transcript	c.4113+47C>T		intron_variant		1	NM_000393.5	ENSP00000364000	P1
COL5A2	ENST00000618828.1 linkuse as main transcript	c.2952+47C>T		intron_variant		5		ENSP00000482184

Frequencies

GnomAD3 genomes

AF:

0.713

AC:

108277

AN:

151826

Hom.:

39682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.822

Gnomad MID

AF:

0.689

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.709

GnomAD3 exomes

AF:

0.733

AC:

151438

AN:

206528

Hom.:

56351

AF XY:

0.737

AC XY:

83026

AN XY:

112646

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.643

Gnomad ASJ exome

AF:

0.717

Gnomad EAS exome

AF:

0.733

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.799

Gnomad OTH exome

AF:

0.738

GnomAD4 exome

AF:

0.785

AC:

1005214

AN:

1280206

Hom.:

398496

Cov.:

AF XY:

0.782

AC XY:

503705

AN XY:

643788

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.643

Gnomad4 ASJ exome

AF:

0.724

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.665

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.760

GnomAD4 genome

AF:

0.713

AC:

108327

AN:

151944

Hom.:

39695

Cov.:

AF XY:

0.712

AC XY:

52897

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.534

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.726

Gnomad4 SAS

AF:

0.673

Gnomad4 FIN

AF:

0.822

Gnomad4 NFE

AF:

0.810

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.727

Hom.:

5219

Bravo

AF:

0.694

Asia WGS

AF:

0.653

AC:

2268

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.27

DANN

Benign

0.27

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