GeneBe

rs773994971

Variant names:

Variant summary

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

The NM_000093.5(COL5A1):​c.76_84delCTGCTGCTG​(p.Leu26_Leu28del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L26L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

COL5A1
NM_000093.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.96

Publications

0 publications found
Variant links:
Genes affected
COL5A1 (HGNC:2209): (collagen type V alpha 1 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. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
COL5A1 Gene-Disease associations (from GenCC):
  • Ehlers-Danlos syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • Ehlers-Danlos syndrome, classic type
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
  • Ehlers-Danlos syndrome, classic type, 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • arterial disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

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
COL5A1NM_000093.5 linkc.76_84delCTGCTGCTG p.Leu26_Leu28del conservative_inframe_deletion Exon 1 of 66 ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkc.76_84delCTGCTGCTG p.Leu26_Leu28del conservative_inframe_deletion Exon 1 of 66 NP_001265003.1 B2ZZ86Q59EE7
COL5A1XM_017014266.3 linkc.76_84delCTGCTGCTG p.Leu26_Leu28del conservative_inframe_deletion Exon 1 of 65 XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkc.76_84delCTGCTGCTG p.Leu26_Leu28del conservative_inframe_deletion Exon 1 of 66 1 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkc.76_84delCTGCTGCTG p.Leu26_Leu28del conservative_inframe_deletion Exon 1 of 66 2 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1120258
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
543268
African (AFR)
AF:
0.00
AC:
0
AN:
22902
American (AMR)
AF:
0.00
AC:
0
AN:
16478
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17140
East Asian (EAS)
AF:
0.00
AC:
0
AN:
23492
South Asian (SAS)
AF:
0.00
AC:
0
AN:
35500
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23322
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3106
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
934352
Other (OTH)
AF:
0.00
AC:
0
AN:
43966
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Jul 14, 2016
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.76_84delCTGCTGCTG variant (also known as p.L26_L28del) is located in coding exon 1 of the COL5A1 gene. This variant results from an in-frame CTGCTGCTG deletion at nucleotide positions 76 to 84. This results in the in-frame deletion of three leucine residues within a poly-leucine track. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 160 samples (320 alleles) with coverage at this position. These amino acid positions are highly conserved on limited sequence alignment. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
Oct 04, 2023
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 3 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.0

Splicing

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

Publications

Other links and lift over

dbSNP: rs773994971; hg19: chr9-137534098; API