rs3740878

Positions:

• chr11-44236252-T-C
• chr11-44236252-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.1936-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,580,138 control chromosomes in the GnomAD database, including 70,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5665 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64842 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.481

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=-0.87).
• BP6: Variant 11-44236252-T-C is Benign according to our data. Variant chr11-44236252-T-C is described in ClinVar as [Benign]. Clinvar id is 263290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.1936-41T>C		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.1936-41T>C		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37388 AN: 151972 Hom.: 5648 Cov.: 32

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.318 AC: 79304 AN: 249662 Hom.: 14531 AF XY: 0.315 AC XY: 42484 AN XY: 134940

Gnomad AFR exome AF: 0.0891

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.434

Gnomad SAS exome AF: 0.371

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.292 AC: 417325 AN: 1428046 Hom.: 64842 Cov.: 24 AF XY: 0.293 AC XY: 208986 AN XY: 712592

Gnomad4 AFR exome AF: 0.0822

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.246 AC: 37424 AN: 152092 Hom.: 5665 Cov.: 32 AF XY: 0.253 AC XY: 18838 AN XY: 74338

Gnomad4 AFR AF: 0.0963

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.270

Alfa AF: 0.257 Hom.: 2569

Bravo AF: 0.246

Asia WGS AF: 0.425 AC: 1476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Exostoses, multiple, type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 17293876, 23052945) -

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	-0.87
CADD	Benign	11
DANN	Benign	0.46

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: rs3740878; hg19: chr11-44257802; COSMIC: COSV59147143; COSMIC: COSV59147143;