rs145343609

Variant names:

• chr6-33165647-C-A
• rs145343609
• NM_080680.3:c.4652G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33165647-C-A
• chr6-33165647-C-G
• chr6-33165647-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080680.3(COL11A2):​c.4652G>T​(p.Arg1551Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.4652G>T	p.Arg1551Leu	missense_variant	Exon 63 of 66	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.4652G>T	p.Arg1551Leu	missense_variant	Exon 63 of 66	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.4394G>T	p.Arg1465Leu	missense_variant	Exon 61 of 64	5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.442G>T		non_coding_transcript_exon_variant	Exon 6 of 9	2
COL11A2	ENST00000683572.1	n.458G>T		non_coding_transcript_exon_variant	Exon 6 of 9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;T;.
Eigen	Benign	0.048
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.59	D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Uncertain	0.11	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Vest4		0.76
MutPred		0.34		.;Gain of glycosylation at S1546 (P = 0.0841);.;
MVP		0.94
MPC		0.42
ClinPred		0.98	D
GERP RS		3.5
gMVP		0.74

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

Other links and lift over

dbSNP: rs145343609; hg19: chr6-33133424; COSMIC: COSV59499185;