6-33163698-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate

The NM_080680.3(COL11A2):​c.5191C>T​(p.Pro1731Ser) 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. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

COL11A2
NM_080680.3 missense

Scores

5
7
5

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.36
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817
BP6
Variant 6-33163698-G-A is Benign according to our data. Variant chr6-33163698-G-A is described in ClinVar as [Benign]. Clinvar id is 2816296.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL11A2NM_080680.3 linkc.5191C>T p.Pro1731Ser missense_variant Exon 66 of 66 ENST00000341947.7 NP_542411.2 P13942A0A0C4DFS1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL11A2ENST00000341947.7 linkc.5191C>T p.Pro1731Ser missense_variant Exon 66 of 66 5 NM_080680.3 ENSP00000339915.2 A0A0C4DFS1
COL11A2ENST00000374708.8 linkc.4933C>T p.Pro1645Ser missense_variant Exon 64 of 64 5 ENSP00000363840.4 Q4VXY6
COL11A2ENST00000477772.1 linkn.981C>T non_coding_transcript_exon_variant Exon 9 of 9 2
COL11A2ENST00000683572.1 linkn.997C>T non_coding_transcript_exon_variant Exon 9 of 9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 17, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.82
D;D;D
MetaSVM
Uncertain
-0.21
T
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.0
D;D;D
REVEL
Pathogenic
0.71
Sift
Benign
0.18
T;T;T
Sift4G
Benign
0.071
T;T;T
Vest4
0.60
MutPred
0.83
.;Gain of catalytic residue at P1731 (P = 0.0235);.;
MVP
0.67
MPC
0.34
ClinPred
0.98
D
GERP RS
4.1
gMVP
0.76

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: chr6-33131475; API