Variant rs3740878 details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.481

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 -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	Protein	UniProt
EXT2	NM_207122.2 linkuse as main transcript	c.1936-41T>C		intron_variant		ENST00000533608.7	NP_997005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7 linkuse as main transcript	c.1936-41T>C		intron_variant		1	NM_207122.2	ENSP00000431173	P1	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37388

AN:

151972

Hom.:

5648

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.293

AC XY:

208986

AN XY:

712592

show subpopulations

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.:

AF XY:

0.253

AC XY:

18838

AN XY:

74338

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 17293876, 23052945) -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

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

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

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