rs200845884
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_000393.5(COL5A2):āc.3542T>Gā(p.Val1181Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 33)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
COL5A2
NM_000393.5 missense
NM_000393.5 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, COL5A2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3083002).
BP6
?
Variant 2-189041677-A-C is Benign according to our data. Variant chr2-189041677-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 576035.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS2
?
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3542T>G | p.Val1181Gly | missense_variant | 50/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3404T>G | p.Val1135Gly | missense_variant | 53/57 | ||
COL5A2 | XM_047443251.1 | c.3404T>G | p.Val1135Gly | missense_variant | 55/59 | ||
COL5A2 | XM_047443252.1 | c.3404T>G | p.Val1135Gly | missense_variant | 54/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3542T>G | p.Val1181Gly | missense_variant | 50/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2381T>G | p.Val794Gly | missense_variant | 43/47 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251380Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135852
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461560Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727108
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GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74512
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 20, 2022 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Uncertain
Sift
Benign
T;.;.
Sift4G
Benign
T;T;.
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at