Variant chr11-44095859-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_207122.2(EXT2):c.-31+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 181,534 control chromosomes in the GnomAD database, including 847 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 726 hom., cov: 34)

Exomes 𝑓: 0.087 ( 121 hom. )

Consequence

EXT2
NM_207122.2 splice_region, intron

Scores

Splicing: ADA: 0.01260

Clinical Significance

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

Conservation

PhyloP100: 1.86

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-44095859-G-T is Benign according to our data. Variant chr11-44095859-G-T is described in ClinVar as [Benign]. Clinvar id is 304569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44095859-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
EXT2	NM_207122.2 linkuse as main transcript	c.-31+7G>T	splice_region_variant, intron_variant	ENST00000533608.7
EXT2	NM_001178083.3 linkuse as main transcript	c.-31+7G>T	splice_region_variant, intron_variant
EXT2	NM_001389630.1 linkuse as main transcript	c.-70+7G>T	splice_region_variant, intron_variant
EXT2	XM_047426529.1 linkuse as main transcript	c.-183+7G>T	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7 linkuse as main transcript	c.-31+7G>T		splice_region_variant, intron_variant		1	NM_207122.2	P1	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.0882

AC:

13414

AN:

152112

Hom.:

725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0530

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0638

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0805

Gnomad OTH

AF:

0.0764

GnomAD4 exome

AF:

0.0871

AC:

2552

AN:

29314

Hom.:

121

Cov.:

AF XY:

0.0890

AC XY:

1330

AN XY:

14946

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0466

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0818

Gnomad4 NFE exome

AF:

0.0863

Gnomad4 OTH exome

AF:

0.0762

GnomAD4 genome

AF:

0.0882

AC:

13423

AN:

152220

Hom.:

726

Cov.:

AF XY:

0.0867

AC XY:

6455

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0529

Gnomad4 ASJ

AF:

0.0893

Gnomad4 EAS

AF:

0.0165

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.0638

Gnomad4 NFE

AF:

0.0805

Gnomad4 OTH

AF:

0.0756

Alfa

AF:

0.0314

Hom.:

Bravo

AF:

0.0861

Asia WGS

AF:

0.0650

AC:

225

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Jun 25, 2020

- -

Exostoses, multiple, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.013

dbscSNV1_RF

Benign

0.030

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