rs121912949

chr6-33174048-G-Achr6-33174048-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2 BP4

The NM_080680.3(COL11A2):c.2492C>T(p.Ser831Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S831S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: COL11A2 NM_080680.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP2: Missense variant where missense usually causes diseases, COL11A2
• BP4: Computational evidence support a benign effect (MetaRNN=0.30917758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3	c.2492C>T	p.Ser831Leu	missense_variant	33/66	ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A2	ENST00000341947.7	c.2492C>T	p.Ser831Leu	missense_variant	33/66	5	NM_080680.3	P4
COL11A2	ENST00000374708.8	c.2234C>T	p.Ser745Leu	missense_variant	31/64	5		A1
COL11A2	ENST00000361917.6	c.1067C>T	p.Ser356Leu	missense_variant	20/24	5
COL11A2	ENST00000477772.1	n.272+2961C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152024 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000720 AC: 18 AN: 249930 Hom.: 0 AF XY: 0.0000665 AC XY: 9 AN XY: 135386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461700 Hom.: 0 Cov.: 37 AF XY: 0.0000344 AC XY: 25 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.000282

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74374

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000221 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000185 AC: 1

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.037	T;T;.
Eigen	Benign	0.028
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.77	N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.32	T;D;T
Sift4G	Benign	0.13	T;T;T
Vest4		0.43
MVP		0.68
MPC		0.63
ClinPred		0.15	T
GERP RS		3.7
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs121912949; hg19: chr6-33141825; COSMIC: COSV59498701; COSMIC: COSV59498701;