12-47980015-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001844.5(COL2A1):c.2673C>G(p.Gly891Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,554,866 control chromosomes in the GnomAD database, including 624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G891G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.016 ( 69 hom., cov: 32)

Exomes 𝑓: 0.018 ( 555 hom. )

Consequence

COL2A1
NM_001844.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.08

Publications

8 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: Ambry Genetics, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
Kniest dysplasia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
platyspondylic dysplasia, Torrance type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
spondyloepimetaphyseal dysplasia, Strudwick type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
spondyloepiphyseal dysplasia congenita
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
spondyloepiphyseal dysplasia with metatarsal shortening
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
spondylometaphyseal dysplasia
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
spondyloperipheral dysplasia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Stickler syndrome type 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Illumina, Orphanet, Genomics England PanelApp
Stickler syndrome, type I, nonsyndromic ocular
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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: Labcorp Genetics (formerly Invitae), Orphanet
otospondylomegaepiphyseal dysplasia, autosomal recessive
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
spondyloepiphyseal dysplasia, Stanescu type
Inheritance: 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: Orphanet, Labcorp Genetics (formerly Invitae)
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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-47980015-G-C is Benign according to our data. Variant chr12-47980015-G-C is described in ClinVar as Benign. ClinVar VariationId is 93789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 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.2673C>G	p.Gly891Gly	synonymous	Exon 40 of 54	NP_001835.3
	COL2A1	NM_033150.3		c.2466C>G	p.Gly822Gly	synonymous	Exon 39 of 53	NP_149162.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL2A1	ENST00000380518.8	TSL:1 MANE Select	c.2673C>G	p.Gly891Gly	synonymous	Exon 40 of 54	ENSP00000369889.3
COL2A1	ENST00000337299.7	TSL:1	c.2466C>G	p.Gly822Gly	synonymous	Exon 39 of 53	ENSP00000338213.6
COL2A1	ENST00000928357.1		c.2676C>G	p.Gly892Gly	synonymous	Exon 40 of 54	ENSP00000598416.1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2363

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0460

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.0208

AC:

3346

AN:

161096

AF XY:

0.0202

show subpopulations

Gnomad AFR exome

AF:

0.00211

Gnomad AMR exome

AF:

0.00334

Gnomad ASJ exome

AF:

0.00339

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0526

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0180

AC:

25185

AN:

1402664

Hom.:

555

Cov.:

AF XY:

0.0175

AC XY:

12087

AN XY:

692354

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

31776

American (AMR)

AF:

0.00349

AC:

127

AN:

36426

Ashkenazi Jewish (ASJ)

AF:

0.00381

AC:

AN:

25192

East Asian (EAS)

AF:

0.138

AC:

4978

AN:

35992

South Asian (SAS)

AF:

0.00408

AC:

324

AN:

79418

European-Finnish (FIN)

AF:

0.0519

AC:

2534

AN:

48860

Middle Eastern (MID)

AF:

0.00861

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0148

AC:

16053

AN:

1081170

Other (OTH)

AF:

0.0165

AC:

960

AN:

58136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1205

2410

3616

4821

6026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.0155

AC:

2363

AN:

152202

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1249

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41548

American (AMR)

AF:

0.00327

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.119

AC:

611

AN:

5156

South Asian (SAS)

AF:

0.00747

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0460

AC:

488

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0151

AC:

1028

AN:

67996

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0104

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (3)

Connective tissue disorder (1)

Stickler syndrome type 1 (1)

Type II Collagenopathies (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.15

(source)

DANN

Benign

0.69

PhyloP100

-3.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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