dbSNP rs117085226: COL5A2:c.403-16T>A (chr2-189097346-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000393.5(COL5A2):c.403-16T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,276 control chromosomes in the GnomAD database, including 563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 44 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 519 hom. )

Consequence

COL5A2
NM_000393.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.417

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-189097346-A-T is Benign according to our data. Variant chr2-189097346-A-T is described in ClinVar as Benign. ClinVar VariationId is 136969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.073 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.403-16T>A		intron	N/A	NP_000384.2	P05997

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.403-16T>A	intron	N/A	ENSP00000364000.3	P05997
COL5A2	ENST00000858728.1		c.400-16T>A	intron	N/A	ENSP00000528787.1
COL5A2	ENST00000858729.1		c.403-16T>A	intron	N/A	ENSP00000528788.1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2240

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0580

Gnomad SAS

AF:

0.0791

Gnomad FIN

AF:

0.00914

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0222

AC:

5590

AN:

251380

AF XY:

0.0239

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.0371

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.00970

AC:

14167

AN:

1461014

Hom.:

519

Cov.:

AF XY:

0.0116

AC XY:

8439

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.0228

AC:

764

AN:

33454

American (AMR)

AF:

0.0382

AC:

1708

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00287

AC:

AN:

26128

East Asian (EAS)

AF:

0.0693

AC:

2749

AN:

39676

South Asian (SAS)

AF:

0.0784

AC:

6760

AN:

86236

European-Finnish (FIN)

AF:

0.00961

AC:

513

AN:

53386

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000685

AC:

761

AN:

1111276

Other (OTH)

AF:

0.0133

AC:

804

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

796

1592

2387

3183

3979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0148

AC:

2251

AN:

152262

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1212

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0212

AC:

881

AN:

41546

American (AMR)

AF:

0.0311

AC:

476

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.0581

AC:

300

AN:

5162

South Asian (SAS)

AF:

0.0795

AC:

384

AN:

4828

European-Finnish (FIN)

AF:

0.00914

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

68030

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

101

203

304

406

507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00678

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.0690

AC:

240

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.9

(source)

DANN

Benign

0.89

PhyloP100

0.42

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over