chr2-189035106-G-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_000393.5(COL5A2):āc.4163C>Gā(p.Thr1388Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1388N) has been classified as Uncertain significance.
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
COL5A2
NM_000393.5 missense
NM_000393.5 missense
Scores
4
8
6
Clinical Significance
Conservation
PhyloP100: 6.78
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, COL5A2
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.4163C>G | p.Thr1388Ser | missense_variant | 53/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.4025C>G | p.Thr1342Ser | missense_variant | 56/57 | ||
COL5A2 | XM_047443251.1 | c.4025C>G | p.Thr1342Ser | missense_variant | 58/59 | ||
COL5A2 | XM_047443252.1 | c.4025C>G | p.Thr1342Ser | missense_variant | 57/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.4163C>G | p.Thr1388Ser | missense_variant | 53/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.3002C>G | p.Thr1001Ser | missense_variant | 46/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152046
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251284Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135818
GnomAD3 exomes
AF:
AC:
2
AN:
251284
Hom.:
AF XY:
AC XY:
2
AN XY:
135818
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461676Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727146
GnomAD4 exome
AF:
AC:
5
AN:
1461676
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
727146
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74270
GnomAD4 genome
AF:
AC:
3
AN:
152046
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74270
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 01, 2021 | This sequence change replaces threonine with serine at codon 1388 of the COL5A2 protein (p.Thr1388Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant has not been reported in the literature in individuals with COL5A2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL5A2 protein function. This variant is present in population databases (rs771415085, ExAC 0.01%). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Uncertain
Sift
Benign
T;.;.
Sift4G
Uncertain
T;T;.
Polyphen
D;.;D
Vest4
MutPred
Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at