6-33167493-G-C

Variant names:

• chr6-33167493-G-C
• rs763995767
• NM_080680.3:c.4055C>G

Variant summary

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

The NM_080680.3(COL11A2):​c.4055C>G​(p.Pro1352Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1352P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL11A2 NM_080680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.85

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 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	c.4055C>G	p.Pro1352Arg	missense_variant	Exon 56 of 66	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.4055C>G	p.Pro1352Arg	missense_variant	Exon 56 of 66	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.3797C>G	p.Pro1266Arg	missense_variant	Exon 54 of 64	5		ENSP00000363840.4
COL11A2	ENST00000683572.1	n.22C>G		non_coding_transcript_exon_variant	Exon 1 of 9
COL11A2	ENST00000477772.1	n.273-1677C>G		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460510 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 726562

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Pathogenic	0.94	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-7.8	D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.029	D;D;D
Vest4		0.48
MutPred		0.50		.;Gain of MoRF binding (P = 0.0038);.;
MVP		0.81
MPC		0.36
ClinPred		1.0	D
GERP RS		4.1
gMVP		0.32

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: rs763995767; hg19: chr6-33135270;