rs1799907

Variant names:

• chr6-33185058-A-T
• rs1799907
• NM_080680.3:c.877-4T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33185058-A-T
• chr6-33185058-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080680.3(COL11A2):​c.877-4T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,548,026 control chromosomes in the GnomAD database, including 77,240 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7749 hom., cov: 31)
  • Exomes 𝑓: 0.31 (69491 hom.)
• Consequence: COL11A2 NM_080680.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006490
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:19
• Conservation: PhyloP100: 0.525
• Publications: 31 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 13

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• otospondylomegaepiphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 53

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• otospondylomegaepiphyseal dysplasia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• otospondylomegaepiphyseal dysplasia, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fibrochondrogenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-33185058-A-T is Benign according to our data. Variant chr6-33185058-A-T is described in ClinVar as Benign. ClinVar VariationId is 46570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080680.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	NM_080680.3	MANE Select	c.877-4T>A		splice_region intron	N/A	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.877-4T>A		splice_region intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.799-4T>A		splice_region intron	N/A	NP_542412.2	Q4VXY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.877-4T>A		splice_region intron	N/A	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.877-4T>A		splice_region intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.799-4T>A		splice_region intron	N/A	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47886 AN: 151790 Hom.: 7746 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.298 AC: 46650 AN: 156324 AF XY: 0.309

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.235

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.312 AC: 435227 AN: 1396118 Hom.: 69491 Cov.: 33 AF XY: 0.315 AC XY: 216676 AN XY: 688746

African (AFR) AF: 0.388 AC: 12251 AN: 31552

American (AMR) AF: 0.218 AC: 7774 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9414 AN: 25166

East Asian (EAS) AF: 0.229 AC: 8189 AN: 35716

South Asian (SAS) AF: 0.386 AC: 30547 AN: 79154

European-Finnish (FIN) AF: 0.218 AC: 10737 AN: 49164

Middle Eastern (MID) AF: 0.375 AC: 2132 AN: 5686

European-Non Finnish (NFE) AF: 0.312 AC: 336048 AN: 1076082

Other (OTH) AF: 0.313 AC: 18135 AN: 57896

GnomAD4 genome AF: 0.315 AC: 47903 AN: 151908 Hom.: 7749 Cov.: 31 AF XY: 0.310 AC XY: 22997 AN XY: 74248

African (AFR) AF: 0.361 AC: 14953 AN: 41416

American (AMR) AF: 0.268 AC: 4097 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1168 AN: 5148

South Asian (SAS) AF: 0.383 AC: 1843 AN: 4808

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10582

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21227 AN: 67904

Other (OTH) AF: 0.321 AC: 674 AN: 2102

Alfa AF: 0.320 Hom.: 2507

Bravo AF: 0.318

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	Fibrochondrogenesis 2 (2)
-	-	2	not provided (2)
-	-	2	Otospondylomegaepiphyseal dysplasia, autosomal dominant (2)
-	-	2	Otospondylomegaepiphyseal dysplasia, autosomal recessive (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 13 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 53 (1)
-	-	1	Connective tissue disorder (1)
-	-	1	Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.53
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs1799907; hg19: chr6-33152835; COSMIC: COSV107403522; COSMIC: COSV107403522;