dbSNP rs11037882: EXT2:c.1080-18T>A (chr11-44130027-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207122.2(EXT2):c.1080-18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,601,054 control chromosomes in the GnomAD database, including 82,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6498 hom., cov: 32)

Exomes 𝑓: 0.31 ( 75688 hom. )

Consequence

EXT2
NM_207122.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.363

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 11-44130027-T-A is Benign according to our data. Variant chr11-44130027-T-A is described in ClinVar as [Benign]. Clinvar id is 198636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44130027-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT2	NM_207122.2 link	c.1080-18T>A		intron_variant	Intron 6 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.1080-18T>A		intron_variant	Intron 6 of 13	1	NM_207122.2	ENSP00000431173.2		Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40838

AN:

151934

Hom.:

6478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.287

GnomAD3 exomes

AF:

0.343

AC:

86193

AN:

251202

Hom.:

17032

AF XY:

0.338

AC XY:

45933

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.458

Gnomad SAS exome

AF:

0.389

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.314

AC:

454857

AN:

1449002

Hom.:

75688

Cov.:

AF XY:

0.315

AC XY:

227214

AN XY:

721714

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.269

AC:

40873

AN:

152052

Hom.:

6498

Cov.:

AF XY:

0.276

AC XY:

20487

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.448

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.265

Hom.:

1092

Bravo

AF:

0.273

Asia WGS

AF:

0.448

AC:

1555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Exostoses, multiple, type 2

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Seizures-scoliosis-macrocephaly syndrome

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Exostoses, multiple, type 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

-0.58

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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