6-33165689-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080680.3(COL11A2):​c.4610C>G​(p.Pro1537Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

COL11A2
NM_080680.3 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13630357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL11A2NM_080680.3 linkc.4610C>G p.Pro1537Arg missense_variant Exon 63 of 66 ENST00000341947.7 NP_542411.2 P13942A0A0C4DFS1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL11A2ENST00000341947.7 linkc.4610C>G p.Pro1537Arg missense_variant Exon 63 of 66 5 NM_080680.3 ENSP00000339915.2 A0A0C4DFS1
COL11A2ENST00000374708.8 linkc.4352C>G p.Pro1451Arg missense_variant Exon 61 of 64 5 ENSP00000363840.4 Q4VXY6
COL11A2ENST00000477772.1 linkn.400C>G non_coding_transcript_exon_variant Exon 6 of 9 2
COL11A2ENST00000683572.1 linkn.416C>G non_coding_transcript_exon_variant Exon 6 of 9

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459094
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
725944
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.014
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T;T;.
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.23
N
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.81
T
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.75
N;N;N
REVEL
Benign
0.24
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.35
T;T;T
Vest4
0.29
MutPred
0.31
.;Gain of methylation at P1537 (P = 0.0297);.;
MVP
0.52
MPC
0.36
ClinPred
0.11
T
GERP RS
3.5
gMVP
0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-33133466; API