2-189110298-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000393.5(COL5A2):c.249C>T(p.Ala83Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,060 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 13 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.34

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-189110298-G-A is Benign according to our data. Variant chr2-189110298-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00622 (946/152194) while in subpopulation AFR AF = 0.0211 (876/41512). AF 95% confidence interval is 0.0199. There are 9 homozygotes in GnomAd4. There are 430 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 946 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.249C>T	p.Ala83Ala	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.249C>T	p.Ala83Ala	synonymous	Exon 2 of 54	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1	TSL:5	c.-382C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 47	ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000858728.1		c.246C>T	p.Ala82Ala	synonymous	Exon 2 of 54	ENSP00000528787.1

Frequencies

GnomAD3 genomes

AF:

0.00621

AC:

945

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00185

AC:

464

AN:

251254

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000835

AC:

1221

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

572

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0235

AC:

786

AN:

33480

American (AMR)

AF:

0.00121

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000139

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000119

AC:

132

AN:

1111996

Other (OTH)

AF:

0.00210

AC:

127

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

135

202

270

337

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:

0.00622

AC:

946

AN:

152194

Hom.:

Cov.:

AF XY:

0.00578

AC XY:

430

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0211

AC:

876

AN:

41512

American (AMR)

AF:

0.00242

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68016

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00366

Hom.:

Bravo

AF:

0.00703

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

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

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

Familial thoracic aortic aneurysm and aortic dissection (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.1

(source)

DANN

Benign

0.80

PhyloP100

-1.3

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