Genetic Variant EXT2:c.-30-80A>C (chr11-44107603-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207122.2(EXT2):c.-30-80A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,373,290 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 232 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-44107603-A-C is Benign according to our data. Variant chr11-44107603-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1327344.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 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.-30-80A>C	intron	N/A	NP_997005.1	Q93063-1
EXT2	NM_000401.3		c.70-80A>C	intron	N/A	NP_000392.3	Q93063-3
EXT2	NM_001178083.3		c.-30-80A>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.-30-80A>C	intron	N/A	ENSP00000431173.2	Q93063-1
EXT2	ENST00000358681.8	TSL:1	c.-30-80A>C	intron	N/A	ENSP00000351509.4	Q93063-2
EXT2	ENST00000343631.4	TSL:1	c.-30-80A>C	intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2279

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.00512

AC:

6246

AN:

1221012

Hom.:

232

AF XY:

0.00482

AC XY:

2921

AN XY:

605714

show subpopulations

African (AFR)

AF:

0.0396

AC:

1089

AN:

27492

American (AMR)

AF:

0.00500

AC:

143

AN:

28574

Ashkenazi Jewish (ASJ)

AF:

0.00870

AC:

171

AN:

19660

East Asian (EAS)

AF:

0.0988

AC:

3755

AN:

38024

South Asian (SAS)

AF:

0.00194

AC:

128

AN:

66050

European-Finnish (FIN)

AF:

0.000137

AC:

AN:

43916

Middle Eastern (MID)

AF:

0.00161

AC:

AN:

4974

European-Non Finnish (NFE)

AF:

0.000525

AC:

494

AN:

940762

Other (OTH)

AF:

0.00877

AC:

452

AN:

51560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

327

654

980

1307

1634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.0150

AC:

2287

AN:

152278

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1116

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0395

AC:

1640

AN:

41522

American (AMR)

AF:

0.00647

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.0780

AC:

404

AN:

5182

South Asian (SAS)

AF:

0.00580

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68030

Other (OTH)

AF:

0.0180

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0107

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

(source)

DANN

Benign

0.62

PhyloP100

0.037

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

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