2-189110286-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000393.5(COL5A2):c.261G>A(p.Thr87Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,614,110 control chromosomes in the GnomAD database, including 18 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. T87T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 17 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.431

Publications

1 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-189110286-C-T is Benign according to our data. Variant chr2-189110286-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.431 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00106 (162/152240) while in subpopulation SAS AF = 0.000621 (3/4828). AF 95% confidence interval is 0.000431. There are 1 homozygotes in GnomAd4. There are 76 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 162 AD gene.

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.261G>A	p.Thr87Thr	synonymous	Exon 2 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.261G>A	p.Thr87Thr	synonymous	Exon 2 of 54	ENSP00000364000.3	P05997
COL5A2	ENST00000858728.1		c.258G>A	p.Thr86Thr	synonymous	Exon 2 of 54	ENSP00000528787.1
COL5A2	ENST00000858729.1		c.261G>A	p.Thr87Thr	synonymous	Exon 2 of 53	ENSP00000528788.1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00175

AC:

439

AN:

251262

AF XY:

0.00184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0273

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000907

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00108

AC:

1580

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

835

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0293

AC:

765

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00122

AC:

105

AN:

86258

European-Finnish (FIN)

AF:

0.000374

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000466

AC:

518

AN:

1111998

Other (OTH)

AF:

0.00253

AC:

153

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00106

AC:

162

AN:

152240

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41532

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00258

Hom.:

Bravo

AF:

0.00119

EpiCase

AF:

0.000872

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (3)

Connective tissue disorder (1)

Ehlers-Danlos syndrome (1)

Ehlers-Danlos syndrome type 7A (1)

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

Ehlers-Danlos syndrome, classic type, 2 (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.3

(source)

DANN

Benign

0.85

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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