rs3740878

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_207122.2(EXT2):c.1936-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,580,138 control chromosomes in the GnomAD database, including 70,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5665 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64842 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.481

Publications

41 publications found

Variant links:

Genes affected

EXT2 (HGNC:3513): (exostosin glycosyltransferase 2) This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

EXT2 Gene-Disease associations (from GenCC):

exostoses, multiple, type 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
seizures-scoliosis-macrocephaly syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
hereditary multiple osteochondromas
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EXT2 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=-0.87).

BP6

Variant 11-44236252-T-C is Benign according to our data. Variant chr11-44236252-T-C is described in ClinVar as Benign. ClinVar VariationId is 263290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT2	NM_207122.2 link	c.1936-41T>C		intron_variant	Intron 12 of 13	ENST00000533608.7	NP_997005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7 link	c.1936-41T>C		intron_variant	Intron 12 of 13	1	NM_207122.2	ENSP00000431173.2

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37388

AN:

151972

Hom.:

5648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0964

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.318

AC:

79304

AN:

249662

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.0891

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.292

AC:

417325

AN:

1428046

Hom.:

64842

Cov.:

AF XY:

0.293

AC XY:

208986

AN XY:

712592

show subpopulations

African (AFR)

AF:

0.0822

AC:

2691

AN:

32742

American (AMR)

AF:

0.520

AC:

23201

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4960

AN:

25918

East Asian (EAS)

AF:

0.398

AC:

15737

AN:

39524

South Asian (SAS)

AF:

0.369

AC:

31579

AN:

85624

European-Finnish (FIN)

AF:

0.307

AC:

16179

AN:

52734

Middle Eastern (MID)

AF:

0.181

AC:

1030

AN:

5702

European-Non Finnish (NFE)

AF:

0.282

AC:

305246

AN:

1081846

Other (OTH)

AF:

0.282

AC:

16702

AN:

59300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16123

32246

48369

64492

80615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10358

20716

31074

41432

51790

<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:

0.246

AC:

37424

AN:

152092

Hom.:

5665

Cov.:

AF XY:

0.253

AC XY:

18838

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0963

AC:

3998

AN:

41506

American (AMR)

AF:

0.415

AC:

6341

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

662

AN:

3462

East Asian (EAS)

AF:

0.414

AC:

2133

AN:

5152

South Asian (SAS)

AF:

0.359

AC:

1733

AN:

4822

European-Finnish (FIN)

AF:

0.315

AC:

3327

AN:

10564

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18310

AN:

67986

Other (OTH)

AF:

0.270

AC:

571

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1372

2744

4116

5488

6860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.254

Hom.:

2921

Bravo

AF:

0.246

Asia WGS

AF:

0.425

AC:

1476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Exostoses, multiple, type 2

Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17293876, 23052945) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Exostoses, multiple, type 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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