dbSNP rs61730262: COL11A2:p.Arg729Pro (chr6-33176287-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080680.3(COL11A2):c.2186G>C(p.Arg729Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,822 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R729Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL11A2
NM_080680.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

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]

COL11A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3 link	c.2186G>C	p.Arg729Pro	missense_variant	Exon 28 of 66	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 link	c.2186G>C	p.Arg729Pro	missense_variant	Exon 28 of 66	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 link	c.1928G>C	p.Arg643Pro	missense_variant	Exon 26 of 64	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000361917.6 link	c.758G>C	p.Arg253Pro	missense_variant	Exon 15 of 24	5		ENSP00000355123.2	H0YIS1
COL11A2	ENST00000477772.1 link	n.272+722G>C		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723190

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

T;T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.052

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Pathogenic

0.67

Sift

Benign

0.071

T;D;D

Sift4G

Benign

0.12

T;T;T

Vest4

0.55

MutPred

0.39

.;Loss of MoRF binding (P = 0.0011);.;

MVP

0.94

MPC

0.63

ClinPred

0.99

GERP RS

4.0

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over