rs4755228

chr11-44107740-C-Achr11-44107740-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_207122.2(EXT2):c.28C>A(p.Arg10=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0156 in 1,614,126 control chromosomes in the GnomAD database, including 1,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (240 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1474 hom.)
• Consequence: EXT2 NM_207122.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.73

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 11-44107740-C-A is Benign according to our data. Variant chr11-44107740-C-A is described in ClinVar as [Benign]. Clinvar id is 195445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44107740-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.28C>A	p.Arg10=	synonymous_variant	2/14	ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.28C>A	p.Arg10=	synonymous_variant	2/14	1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2925 AN: 152134 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0354 AC: 8899 AN: 251388 Hom.: 797 AF XY: 0.0343 AC XY: 4667 AN XY: 135866

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.0355

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.0458

Gnomad FIN exome AF: 0.0150

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0153 AC: 22314 AN: 1461874 Hom.: 1474 Cov.: 32 AF XY: 0.0161 AC XY: 11688 AN XY: 727242

Gnomad4 AFR exome AF: 0.00349

Gnomad4 AMR exome AF: 0.0353

Gnomad4 ASJ exome AF: 0.00627

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00401

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0192 AC: 2925 AN: 152252 Hom.: 240 Cov.: 32 AF XY: 0.0219 AC XY: 1627 AN XY: 74436

Gnomad4 AFR AF: 0.00452

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.0603

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.00447

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00814 Hom.: 141

Bravo AF: 0.0208

Asia WGS AF: 0.132 AC: 457 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:6

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)	Oct 20, 2014	- -

Exostoses, multiple, type 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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

Mar 03, 2015

- -

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	-0.16
Cadd	Benign	13
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs4755228; hg19: chr11-44129290; COSMIC: COSV59149768; COSMIC: COSV59149768;