NM_000393.5:c.3690A>C

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.3690A>C(p.Thr1230Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,802 control chromosomes in the GnomAD database, including 9,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1230T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.096 ( 739 hom., cov: 31)

Exomes 𝑓: 0.10 ( 8510 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.99

Publications

13 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=-0.56).

BP6

Variant 2-189039507-T-G is Benign according to our data. Variant chr2-189039507-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.3690A>C	p.Thr1230Thr	synonymous	Exon 51 of 54	NP_000384.2	P05997

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.3690A>C	p.Thr1230Thr	synonymous	Exon 51 of 54	ENSP00000364000.3	P05997
COL5A2	ENST00000858728.1		c.3687A>C	p.Thr1229Thr	synonymous	Exon 51 of 54	ENSP00000528787.1
COL5A2	ENST00000858729.1		c.3582A>C	p.Thr1194Thr	synonymous	Exon 50 of 53	ENSP00000528788.1

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14627

AN:

152002

Hom.:

739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0721

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0990

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0892

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.106

AC:

26624

AN:

250522

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.0719

Gnomad AMR exome

AF:

0.0659

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0900

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.104

AC:

151413

AN:

1461682

Hom.:

8510

Cov.:

AF XY:

0.106

AC XY:

77299

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.0732

AC:

2451

AN:

33478

American (AMR)

AF:

0.0714

AC:

3194

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4383

AN:

26132

East Asian (EAS)

AF:

0.145

AC:

5767

AN:

39692

South Asian (SAS)

AF:

0.160

AC:

13817

AN:

86238

European-Finnish (FIN)

AF:

0.0931

AC:

4970

AN:

53386

Middle Eastern (MID)

AF:

0.172

AC:

986

AN:

5728

European-Non Finnish (NFE)

AF:

0.0983

AC:

109311

AN:

1111922

Other (OTH)

AF:

0.108

AC:

6534

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

8056

16112

24168

32224

40280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3998

7996

11994

15992

19990

<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:

0.0962

AC:

14632

AN:

152120

Hom.:

739

Cov.:

AF XY:

0.0976

AC XY:

7262

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0723

AC:

3003

AN:

41522

American (AMR)

AF:

0.0989

AC:

1512

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

599

AN:

3466

East Asian (EAS)

AF:

0.119

AC:

615

AN:

5156

South Asian (SAS)

AF:

0.151

AC:

726

AN:

4812

European-Finnish (FIN)

AF:

0.0892

AC:

944

AN:

10588

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6913

AN:

67968

Other (OTH)

AF:

0.105

AC:

222

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

677

1354

2032

2709

3386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.105

Hom.:

1500

Bravo

AF:

0.0944

Asia WGS

AF:

0.126

AC:

437

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.117

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Ehlers-Danlos syndrome, classic type, 2 (2)

not provided (2)

Ehlers-Danlos syndrome type 7A (1)

Ehlers-Danlos syndrome, classic type, 1 (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.89

(source)

DANN

Benign

0.70

PhyloP100

-2.0

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over