Variant chr2-189100165-A-G 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.337-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,596,518 control chromosomes in the GnomAD database, including 16,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1368 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15444 hom. )

Consequence

COL5A2
NM_000393.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.71

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=-1.04).

BP6

Variant 2-189100165-A-G is Benign according to our data. Variant chr2-189100165-A-G is described in ClinVar as [Benign]. Clinvar id is 256000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
COL5A2	NM_000393.5 linkuse as main transcript	c.337-26T>C	intron_variant	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 linkuse as main transcript	c.199-26T>C	intron_variant		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.199-26T>C	intron_variant		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.199-26T>C	intron_variant		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 linkuse as main transcript	c.337-26T>C	intron_variant	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1 linkuse as main transcript	c.-294-26T>C	intron_variant	5		ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000649966.1 linkuse as main transcript	c.199-26T>C	intron_variant			ENSP00000496785.1	A0A3B3IRH9

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20196

AN:

151996

Hom.:

1371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0982

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0978

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.141

AC:

35211

AN:

250192

Hom.:

2726

AF XY:

0.147

AC XY:

19843

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.0949

Gnomad AMR exome

AF:

0.0947

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.142

AC:

205174

AN:

1444404

Hom.:

15444

Cov.:

AF XY:

0.145

AC XY:

103996

AN XY:

719470

show subpopulations

Gnomad4 AFR exome

AF:

0.0916

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.133

AC:

20189

AN:

152114

Hom.:

1368

Cov.:

AF XY:

0.134

AC XY:

9957

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0982

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.0973

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.149

Hom.:

339

Bravo

AF:

0.129

Asia WGS

AF:

0.137

AC:

474

AN:

3474

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 23, 2018	- -
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

- -

Ehlers-Danlos syndrome, classic type, 2

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

-1.0

CADD

Benign

0.013

DANN

Benign

0.31

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