Genetic Variant EXT2:c.-31+496T>G (chr11-44096348-T-G) – 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.-31+496T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,531,358 control chromosomes in the GnomAD database, including 395,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 37746 hom., cov: 28)

Exomes 𝑓: 0.72 ( 358250 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.96

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 links:

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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 11-44096348-T-G is Benign according to our data. Variant chr11-44096348-T-G is described in ClinVar as [Benign]. Clinvar id is 1287445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44096348-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT2	NM_207122.2 link	c.-31+496T>G		intron_variant	Intron 1 of 13	ENST00000533608.7	NP_997005.1	Q93063-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7 link	c.-31+496T>G		intron_variant	Intron 1 of 13	1	NM_207122.2	ENSP00000431173.2		Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.706

AC:

106253

AN:

150574

Hom.:

37705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.710

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.712

GnomAD2 exomes

AF:

0.751

AC:

101402

AN:

134962

AF XY:

0.748

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.849

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.923

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.710

Gnomad OTH exome

AF:

0.735

GnomAD4 exome

AF:

0.719

AC:

992320

AN:

1380666

Hom.:

358250

Cov.:

AF XY:

0.719

AC XY:

489668

AN XY:

681166

show subpopulations

Gnomad4 AFR exome

AF:

0.604

AC:

19000

AN:

31464

Gnomad4 AMR exome

AF:

0.844

AC:

30053

AN:

35622

Gnomad4 ASJ exome

AF:

0.685

AC:

17186

AN:

25080

Gnomad4 EAS exome

AF:

0.904

AC:

32213

AN:

35630

Gnomad4 SAS exome

AF:

0.731

AC:

57857

AN:

79108

Gnomad4 FIN exome

AF:

0.773

AC:

26158

AN:

33838

Gnomad4 NFE exome

AF:

0.710

AC:

764854

AN:

1076842

Gnomad4 Remaining exome

AF:

0.716

AC:

41322

AN:

57748

Heterozygous variant carriers

14543

29086

43629

58172

72715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

19466

38932

58398

77864

97330

<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:

0.706

AC:

106352

AN:

150692

Hom.:

37746

Cov.:

AF XY:

0.713

AC XY:

52456

AN XY:

73610

show subpopulations

Gnomad4 AFR

AF:

0.616

AC:

0.615532

AN:

0.615532

Gnomad4 AMR

AF:

0.798

AC:

0.797555

AN:

0.797555

Gnomad4 ASJ

AF:

0.687

AC:

0.687283

AN:

0.687283

Gnomad4 EAS

AF:

0.911

AC:

0.910841

AN:

0.910841

Gnomad4 SAS

AF:

0.737

AC:

0.737098

AN:

0.737098

Gnomad4 FIN

AF:

0.778

AC:

0.778

AN:

0.778

Gnomad4 NFE

AF:

0.711

AC:

0.711269

AN:

0.711269

Gnomad4 OTH

AF:

0.714

AC:

0.714354

AN:

0.714354

Heterozygous variant carriers

1585

3170

4755

6340

7925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.662

Hom.:

4056

Bravo

AF:

0.701

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 27, 2018

GeneDx

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

-0.88

CADD

Benign

2.1

DANN

Benign

0.52

Mutation Taster

=14/86

disease causing (long InDel)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over