GeneBe

2-189092293-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000393.5(COL5A2):​c.567+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.5e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

COL5A2
NM_000393.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A2NM_000393.5 linkc.567+17G>A intron_variant Intron 7 of 53 ENST00000374866.9 NP_000384.2 P05997
COL5A2XM_011510573.4 linkc.429+17G>A intron_variant Intron 10 of 56 XP_011508875.1
COL5A2XM_047443251.1 linkc.429+17G>A intron_variant Intron 12 of 58 XP_047299207.1
COL5A2XM_047443252.1 linkc.429+17G>A intron_variant Intron 11 of 57 XP_047299208.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A2ENST00000374866.9 linkc.567+17G>A intron_variant Intron 7 of 53 1 NM_000393.5 ENSP00000364000.3 P05997
COL5A2ENST00000618828.1 linkc.-64+17G>A intron_variant Intron 7 of 46 5 ENSP00000482184.1 A0A087WYX9
COL5A2ENST00000649966.1 linkc.429+17G>A intron_variant Intron 7 of 10 ENSP00000496785.1 A0A3B3IRH9

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.48e-7
AC:
1
AN:
1337136
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
669252
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31008
American (AMR)
AF:
0.00
AC:
0
AN:
42274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24968
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38484
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80722
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52170
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5522
European-Non Finnish (NFE)
AF:
9.94e-7
AC:
1
AN:
1005810
Other (OTH)
AF:
0.00
AC:
0
AN:
56178
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74304
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41416
American (AMR)
AF:
0.00
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
4.2
DANN
Benign
0.72
PhyloP100
-0.018

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

Other links and lift over

dbSNP: rs780672109; hg19: chr2-189957019; API