rs1799912

Variant names:

• chr6-33164916-C-G
• NM_080680.3:c.4799G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-33164916-C-G
• chr6-33164916-C-T

Variant summary

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

The NM_080680.3(COL11A2):​c.4799G>C​(p.Arg1600Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,429,222 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. R1600Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COL11A2 NM_080680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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.4799G>C	p.Arg1600Pro	missense_variant	Exon 64 of 66	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.4799G>C	p.Arg1600Pro	missense_variant	Exon 64 of 66	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.4541G>C	p.Arg1514Pro	missense_variant	Exon 62 of 64	5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.589G>C		non_coding_transcript_exon_variant	Exon 7 of 9	2
COL11A2	ENST00000683572.1	n.605G>C		non_coding_transcript_exon_variant	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1429222 Hom.: 0 Cov.: 32 AF XY: 0.00000283 AC XY: 2 AN XY: 707742

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: 0.0000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

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	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.50	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Vest4		0.61
MutPred		0.57		.;Loss of methylation at R1600 (P = 0.0447);.;
MVP		0.82
MPC		0.49
ClinPred		0.96	D
GERP RS		2.9
gMVP		0.89

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: chr6-33132693;