2-189043211-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000393.5(COL5A2):c.3411T>C(p.Gly1137Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,613,866 control chromosomes in the GnomAD database, including 762,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70265 hom., cov: 30)

Exomes 𝑓: 0.97 ( 692073 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.09

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Ehlers-Danlos syndrome, classic type, 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

COL5A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-189043211-A-G is Benign according to our data. Variant chr2-189043211-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5 link	c.3411T>C	p.Gly1137Gly	synonymous_variant	Exon 48 of 54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.3273T>C	p.Gly1091Gly	synonymous_variant	Exon 51 of 57		XP_011508875.1
COL5A2	XM_047443251.1 link	c.3273T>C	p.Gly1091Gly	synonymous_variant	Exon 53 of 59		XP_047299207.1
COL5A2	XM_047443252.1 link	c.3273T>C	p.Gly1091Gly	synonymous_variant	Exon 52 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9 link	c.3411T>C	p.Gly1137Gly	synonymous_variant	Exon 48 of 54	1	NM_000393.5	ENSP00000364000.3		P05997
COL5A2	ENST00000618828.1 link	c.2250T>C	p.Gly750Gly	synonymous_variant	Exon 41 of 47	5		ENSP00000482184.1		A0A087WYX9

Frequencies

GnomAD3 genomes

AF:

0.960

AC:

146094

AN:

152136

Hom.:

70210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.919

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.971

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.981

Gnomad OTH

AF:

0.959

GnomAD2 exomes

AF:

0.950

AC:

238595

AN:

251182

AF XY:

0.956

show subpopulations

Gnomad AFR exome

AF:

0.949

Gnomad AMR exome

AF:

0.842

Gnomad ASJ exome

AF:

0.972

Gnomad EAS exome

AF:

0.912

Gnomad FIN exome

AF:

0.950

Gnomad NFE exome

AF:

0.981

Gnomad OTH exome

AF:

0.957

GnomAD4 exome

AF:

0.973

AC:

1421624

AN:

1461614

Hom.:

692073

Cov.:

AF XY:

0.973

AC XY:

707732

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.946

AC:

31679

AN:

33474

American (AMR)

AF:

0.849

AC:

37973

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.972

AC:

25403

AN:

26132

East Asian (EAS)

AF:

0.886

AC:

35144

AN:

39684

South Asian (SAS)

AF:

0.972

AC:

83824

AN:

86222

European-Finnish (FIN)

AF:

0.953

AC:

50926

AN:

53410

Middle Eastern (MID)

AF:

0.966

AC:

5557

AN:

5752

European-Non Finnish (NFE)

AF:

0.983

AC:

1092560

AN:

1111852

Other (OTH)

AF:

0.970

AC:

58558

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1846

3693

5539

7386

9232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21646

43292

64938

86584

108230

<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:

0.960

AC:

146207

AN:

152252

Hom.:

70265

Cov.:

AF XY:

0.959

AC XY:

71359

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.947

AC:

39345

AN:

41544

American (AMR)

AF:

0.919

AC:

14050

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.975

AC:

3385

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4705

AN:

5170

South Asian (SAS)

AF:

0.972

AC:

4683

AN:

4820

European-Finnish (FIN)

AF:

0.948

AC:

10063

AN:

10614

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.981

AC:

66750

AN:

68024

Other (OTH)

AF:

0.960

AC:

2027

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

289

578

868

1157

1446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.969

Hom.:

113534

Bravo

AF:

0.954

Asia WGS

AF:

0.958

AC:

3333

AN:

3478

EpiCase

AF:

0.979

EpiControl

AF:

0.977

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BA1 -

Ehlers-Danlos syndrome, classic type, 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

(source)

DANN

Benign

0.50

PhyloP100

1.1

Mutation Taster

=77/23

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over