2-189110232-G-T

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.315C>A(p.Thr105Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,612,522 control chromosomes in the GnomAD database, including 746,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66285 hom., cov: 31)

Exomes 𝑓: 0.96 ( 680320 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.524

Publications

21 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=-0.77).

BP6

Variant 2-189110232-G-T is Benign according to our data. Variant chr2-189110232-G-T is described in ClinVar as Benign. ClinVar VariationId is 439539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.524 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.315C>A	p.Thr105Thr	synonymous_variant	Exon 2 of 54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 5 of 57		XP_011508875.1
COL5A2	XM_047443251.1 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 7 of 59		XP_047299207.1
COL5A2	XM_047443252.1 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 6 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 link	c.315C>A	p.Thr105Thr	synonymous_variant	Exon 2 of 54	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000649966.1 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 2 of 11			ENSP00000496785.1	A0A3B3IRH9
COL5A2	ENST00000618828.1 link	c.-316C>A		5_prime_UTR_variant	Exon 2 of 47	5		ENSP00000482184.1	A0A087WYX9

Frequencies

GnomAD3 genomes

AF:

0.931

AC:

141673

AN:

152098

Hom.:

66260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.990

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.981

Gnomad OTH

AF:

0.931

GnomAD2 exomes

AF:

0.930

AC:

233806

AN:

251280

AF XY:

0.935

show subpopulations

Gnomad AFR exome

AF:

0.856

Gnomad AMR exome

AF:

0.799

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

0.918

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.980

Gnomad OTH exome

AF:

0.943

GnomAD4 exome

AF:

0.964

AC:

1407881

AN:

1460306

Hom.:

680320

Cov.:

AF XY:

0.963

AC XY:

699557

AN XY:

726558

show subpopulations

African (AFR)

AF:

0.853

AC:

28528

AN:

33430

American (AMR)

AF:

0.805

AC:

36006

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

25326

AN:

26130

East Asian (EAS)

AF:

0.869

AC:

34478

AN:

39692

South Asian (SAS)

AF:

0.890

AC:

76703

AN:

86208

European-Finnish (FIN)

AF:

0.988

AC:

52796

AN:

53420

Middle Eastern (MID)

AF:

0.956

AC:

5329

AN:

5574

European-Non Finnish (NFE)

AF:

0.982

AC:

1091081

AN:

1110796

Other (OTH)

AF:

0.955

AC:

57634

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2552

5104

7655

10207

12759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21600

43200

64800

86400

108000

<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:

0.931

AC:

141747

AN:

152216

Hom.:

66285

Cov.:

AF XY:

0.931

AC XY:

69255

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.857

AC:

35561

AN:

41514

American (AMR)

AF:

0.880

AC:

13442

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3377

AN:

3472

East Asian (EAS)

AF:

0.906

AC:

4686

AN:

5172

South Asian (SAS)

AF:

0.889

AC:

4286

AN:

4822

European-Finnish (FIN)

AF:

0.990

AC:

10513

AN:

10622

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.981

AC:

66721

AN:

68028

Other (OTH)

AF:

0.930

AC:

1965

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

469

937

1406

1874

2343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.961

Hom.:

97947

Bravo

AF:

0.918

Asia WGS

AF:

0.897

AC:

3121

AN:

3478

EpiCase

AF:

0.979

EpiControl

AF:

0.976

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, classic type, 2

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

-0.77

CADD

Benign

6.9

(source)

DANN

Benign

0.66

PhyloP100

-0.52

Mutation Taster

=100/0

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