rs2855425

Variant names:

• chr6-33176596-G-A
• rs2855425
• NM_080680.3:c.2116-110C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33176596-G-A
• chr6-33176596-G-C
• chr6-33176596-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080680.3(COL11A2):​c.2116-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,396,414 control chromosomes in the GnomAD database, including 391,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (47196 hom., cov: 31)
  • Exomes 𝑓: 0.74 (344193 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.491

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-33176596-G-A is Benign according to our data. Variant chr6-33176596-G-A is described in ClinVar as [Benign]. Clinvar id is 1273987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.2116-110C>T		intron_variant	Intron 26 of 65	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.2116-110C>T		intron_variant	Intron 26 of 65	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.1858-110C>T		intron_variant	Intron 24 of 63	5		ENSP00000363840.4
COL11A2	ENST00000361917.6	c.688-110C>T		intron_variant	Intron 13 of 23	5		ENSP00000355123.2
COL11A2	ENST00000477772.1	n.272+413C>T		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119019 AN: 151918 Hom.: 47152 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.740 AC: 920888 AN: 1244378 Hom.: 344193 Cov.: 17 AF XY: 0.745 AC XY: 466368 AN XY: 626102

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.811

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.889

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.760

GnomAD4 genome AF: 0.783 AC: 119119 AN: 152036 Hom.: 47196 Cov.: 31 AF XY: 0.785 AC XY: 58311 AN XY: 74300

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.800

Alfa AF: 0.744 Hom.: 79787

Bravo AF: 0.794

Asia WGS AF: 0.901 AC: 3132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.77

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: rs2855425; hg19: chr6-33144373;