rs3829735

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001844.5(COL2A1):c.2193+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,581,386 control chromosomes in the GnomAD database, including 945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 68 hom., cov: 33)

Exomes 𝑓: 0.012 ( 877 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.50

Publications

5 publications found

Variant links:

Genes affected

COL2A1 (HGNC:2200): (collagen type II alpha 1 chain) This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]

COL2A1 Gene-Disease associations (from GenCC):

achondrogenesis type II
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
COL2A1-related spondyloepiphyseal dysplasia
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dysplasia of the proximal femoral epiphyses
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Kniest dysplasia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
platyspondylic dysplasia, Torrance type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
spondyloepimetaphyseal dysplasia, Strudwick type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
spondyloepiphyseal dysplasia congenita
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen
spondyloepiphyseal dysplasia with metatarsal shortening
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
spondylometaphyseal dysplasia
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
spondyloperipheral dysplasia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Stickler syndrome type 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Illumina
Stickler syndrome, type I, nonsyndromic ocular
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
avascular necrosis of femoral head, primary, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Legg-Calve-Perthes disease
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
otospondylomegaepiphyseal dysplasia, autosomal recessive
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
spondyloepiphyseal dysplasia, Stanescu type
Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
autosomal dominant rhegmatogenous retinal detachment
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dysspondyloenchondromatosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial avascular necrosis of femoral head
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypochondrogenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
multiple epiphyseal dysplasia, Beighton type
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
spondylometaphyseal dysplasia, Schmidt type
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
otospondylomegaepiphyseal dysplasia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
vitreoretinopathy with phalangeal epiphyseal dysplasia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

COL2A1 links:

LOC105369752 (HGNC:):

LOC105369752 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-47982816-C-T is Benign according to our data. Variant chr12-47982816-C-T is described in ClinVar as Benign. ClinVar VariationId is 258224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001844.5. 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
	COL2A1	NM_001844.5	MANE Select	c.2193+32G>A		intron	N/A	NP_001835.3
	COL2A1	NM_033150.3		c.1986+32G>A		intron	N/A	NP_149162.2	P02458-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL2A1	ENST00000380518.8	TSL:1 MANE Select	c.2193+32G>A	intron	N/A	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7	TSL:1	c.1986+32G>A	intron	N/A	ENSP00000338213.6	P02458-1
COL2A1	ENST00000928357.1		c.2196+32G>A	intron	N/A	ENSP00000598416.1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1753

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00883

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0254

AC:

6193

AN:

243420

AF XY:

0.0301

show subpopulations

Gnomad AFR exome

AF:

0.00967

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00890

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0000604

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0120

AC:

17093

AN:

1429088

Hom.:

877

Cov.:

AF XY:

0.0151

AC XY:

10788

AN XY:

712968

show subpopulations

African (AFR)

AF:

0.00856

AC:

282

AN:

32930

American (AMR)

AF:

0.00331

AC:

148

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

247

AN:

25960

East Asian (EAS)

AF:

0.0955

AC:

3783

AN:

39592

South Asian (SAS)

AF:

0.112

AC:

9646

AN:

85756

European-Finnish (FIN)

AF:

0.000108

AC:

AN:

46464

Middle Eastern (MID)

AF:

0.0505

AC:

288

AN:

5708

European-Non Finnish (NFE)

AF:

0.00148

AC:

1606

AN:

1088504

Other (OTH)

AF:

0.0183

AC:

1088

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1027

2053

3080

4106

5133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0115

AC:

1750

AN:

152298

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1053

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00883

AC:

367

AN:

41558

American (AMR)

AF:

0.00536

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3468

East Asian (EAS)

AF:

0.0996

AC:

515

AN:

5172

South Asian (SAS)

AF:

0.116

AC:

561

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00238

AC:

162

AN:

68030

Other (OTH)

AF:

0.0119

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00997

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.057

(source)

DANN

Benign

0.49

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over