dbSNP rs11037909: EXT2:c.1807-51T>C (chr11-44234064-T-C) – ACMG Classification: Benign (-20 pts)

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.1807-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,611,356 control chromosomes in the GnomAD database, including 72,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5937 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66175 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.957

Publications

30 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, Ambry Genetics
seizures-scoliosis-macrocephaly syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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=-0.88).

BP6

Variant 11-44234064-T-C is Benign according to our data. Variant chr11-44234064-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207122.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EXT2	NM_207122.2	MANE Select	c.1807-51T>C	intron	N/A	NP_997005.1	Q93063-1
EXT2	NM_000401.3		c.1906-51T>C	intron	N/A	NP_000392.3	Q93063-3
EXT2	NM_001178083.3		c.1837-51T>C	intron	N/A	NP_001171554.1	Q93063-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EXT2	ENST00000533608.7	TSL:1 MANE Select	c.1807-51T>C	intron	N/A	ENSP00000431173.2	Q93063-1
EXT2	ENST00000358681.8	TSL:1	c.1837-51T>C	intron	N/A	ENSP00000351509.4	Q93063-2
EXT2	ENST00000343631.4	TSL:1	c.1807-51T>C	intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39596

AN:

152038

Hom.:

5917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.321

AC:

80056

AN:

249572

AF XY:

0.317

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.293

AC:

427449

AN:

1459200

Hom.:

66175

Cov.:

AF XY:

0.294

AC XY:

213263

AN XY:

725990

show subpopulations

African (AFR)

AF:

0.133

AC:

4447

AN:

33426

American (AMR)

AF:

0.521

AC:

23270

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4987

AN:

26110

East Asian (EAS)

AF:

0.394

AC:

15616

AN:

39636

South Asian (SAS)

AF:

0.368

AC:

31705

AN:

86116

European-Finnish (FIN)

AF:

0.307

AC:

16373

AN:

53268

Middle Eastern (MID)

AF:

0.180

AC:

981

AN:

5462

European-Non Finnish (NFE)

AF:

0.282

AC:

312943

AN:

1110292

Other (OTH)

AF:

0.284

AC:

17127

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14203

28406

42608

56811

71014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10732

21464

32196

42928

53660

<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:

0.261

AC:

39642

AN:

152156

Hom.:

5937

Cov.:

AF XY:

0.267

AC XY:

19900

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.149

AC:

6188

AN:

41528

American (AMR)

AF:

0.418

AC:

6383

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3472

East Asian (EAS)

AF:

0.412

AC:

2128

AN:

5162

South Asian (SAS)

AF:

0.358

AC:

1729

AN:

4830

European-Finnish (FIN)

AF:

0.315

AC:

3335

AN:

10598

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18285

AN:

67974

Other (OTH)

AF:

0.275

AC:

580

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1422

2844

4266

5688

7110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.263

Hom.:

7666

Bravo

AF:

0.263

Asia WGS

AF:

0.431

AC:

1497

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Exostoses, multiple, type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.6

(source)

DANN

Benign

0.84

PhyloP100

-0.96

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