rs387906556

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_080680.3(COL11A2):​c.2864G>A​(p.Gly955Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

COL11A2
NM_080680.3 missense

Scores

13
2
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86
Variant links:
Genes affected
COL11A2 (HGNC:2187): (collagen type XI alpha 2 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6. [provided by RefSeq, Jul 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL11A2NM_080680.3 linkc.2864G>A p.Gly955Glu missense_variant Exon 39 of 66 ENST00000341947.7 NP_542411.2 P13942A0A0C4DFS1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL11A2ENST00000341947.7 linkc.2864G>A p.Gly955Glu missense_variant Exon 39 of 66 5 NM_080680.3 ENSP00000339915.2 A0A0C4DFS1
COL11A2ENST00000374708.8 linkc.2606G>A p.Gly869Glu missense_variant Exon 37 of 64 5 ENSP00000363840.4 Q4VXY6
COL11A2ENST00000477772.1 linkn.272+4445G>A intron_variant Intron 5 of 8 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.090
T;T;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Pathogenic
0.87
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Pathogenic
0.99
D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.7
D;D;D
REVEL
Pathogenic
0.99
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Vest4
0.87
MutPred
0.99
.;Gain of solvent accessibility (P = 0.0012);.;
MVP
0.98
MPC
1.2
ClinPred
1.0
D
GERP RS
4.8
gMVP
0.99

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs387906556; hg19: chr6-33140341; API