rs760530147

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001844.5(COL2A1):c.1123-29_1123-27delTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,577,276 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.840

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 12-47987735-TGAA-T is Benign according to our data. Variant chr12-47987735-TGAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258205.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5 link	c.1123-29_1123-27delTTC		intron_variant	Intron 18 of 53	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL2A1	ENST00000380518.8 link	c.1123-29_1123-27delTTC	intron_variant	Intron 18 of 53	1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7 link	c.916-29_916-27delTTC	intron_variant	Intron 17 of 52	1		ENSP00000338213.6
COL2A1	ENST00000493991.5 link	n.47-29_47-27delTTC	intron_variant	Intron 1 of 36	2

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000401

AC:

AN:

214522

AF XY:

0.000379

show subpopulations

Gnomad AFR exome

AF:

0.0000781

Gnomad AMR exome

AF:

0.000154

Gnomad ASJ exome

AF:

0.00621

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000914

GnomAD4 exome

AF:

0.000267

AC:

380

AN:

1425468

Hom.:

AF XY:

0.000282

AC XY:

200

AN XY:

708518

show subpopulations

African (AFR)

AF:

0.0000614

AC:

AN:

32594

American (AMR)

AF:

0.000139

AC:

AN:

43194

Ashkenazi Jewish (ASJ)

AF:

0.00632

AC:

162

AN:

25632

East Asian (EAS)

AF:

0.00

AC:

AN:

38692

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.000171

AC:

186

AN:

1085180

Other (OTH)

AF:

0.000390

AC:

AN:

58960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000231

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

41278

American (AMR)

AF:

0.000197

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00126

Hom.:

Bravo

AF:

0.000246

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.84

La Branchor

0.88

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over