GeneBe

2-189079109-TAA-TAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000393.5(COL5A2):​c.961-4_961-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,401,912 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

COL5A2
NM_000393.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A2NM_000393.5 linkc.961-4_961-3dupTT splice_region_variant, intron_variant Intron 14 of 53 ENST00000374866.9 NP_000384.2 P05997
COL5A2XM_011510573.4 linkc.823-4_823-3dupTT splice_region_variant, intron_variant Intron 17 of 56 XP_011508875.1
COL5A2XM_047443251.1 linkc.823-4_823-3dupTT splice_region_variant, intron_variant Intron 19 of 58 XP_047299207.1
COL5A2XM_047443252.1 linkc.823-4_823-3dupTT splice_region_variant, intron_variant Intron 18 of 57 XP_047299208.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A2ENST00000374866.9 linkc.961-3_961-2insTT splice_region_variant, intron_variant Intron 14 of 53 1 NM_000393.5 ENSP00000364000.3 P05997
COL5A2ENST00000618828.1 linkc.331-3_331-2insTT splice_region_variant, intron_variant Intron 14 of 46 5 ENSP00000482184.1 A0A087WYX9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000285
AC:
4
AN:
1401912
Hom.:
0
Cov.:
29
AF XY:
0.00000286
AC XY:
2
AN XY:
698244
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31590
American (AMR)
AF:
0.00
AC:
0
AN:
42298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24830
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37758
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83002
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51812
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5516
European-Non Finnish (NFE)
AF:
0.00000281
AC:
3
AN:
1067440
Other (OTH)
AF:
0.0000173
AC:
1
AN:
57666
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.225
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.2
Mutation Taster
=96/4
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs542134887; hg19: chr2-189943835; API