Variant chr11-44096348-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EXT2	NM_207122.2 linkuse as main transcript	c.-31+496T>G		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7 linkuse as main transcript	c.-31+496T>G		intron_variant		1	NM_207122.2	P1	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

GnomAD3 exomes

AF:

0.751

AC:

101402

AN:

134962

Hom.:

38648

AF XY:

0.748

AC XY:

54782

AN XY:

73282

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 SAS exome

AF:

0.730

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

Gnomad4 AMR exome

AF:

0.844

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.904

Gnomad4 SAS exome

AF:

0.731

Gnomad4 FIN exome

AF:

0.773

Gnomad4 NFE exome

AF:

0.710

Gnomad4 OTH exome

AF:

0.716

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

Gnomad4 AMR

AF:

0.798

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.778

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.714

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.1

DANN

Benign

0.52

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