rs11037882

chr11-44130027-T-Achr11-44130027-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.363

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]

ACMG classification

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/exons	MANE	UniProt
EXT2	NM_207122.2	c.1080-18T>A		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.1080-18T>A		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40838 AN: 151934 Hom.: 6478 Cov.: 32

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

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.: 29 AF XY: 0.315 AC XY: 227214 AN XY: 721714

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.: 32 AF XY: 0.276 AC XY: 20487 AN XY: 74308

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 17, 2014	- -

Exostoses, multiple, type 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Seizures-scoliosis-macrocephaly syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Exostoses, multiple, type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs11037882; hg19: chr11-44151577; COSMIC: COSV59147132; COSMIC: COSV59147132;