11-44096348-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207122.2(EXT2):c.-31+496T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,531,358 control chromosomes in the GnomAD database, including 395,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (37746 hom., cov: 28)
  • Exomes 𝑓: 0.72 (358250 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.96

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-44096348-T-G is Benign according to our data. Variant chr11-44096348-T-G is described in ClinVar as [Benign]. Clinvar id is 1287445.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-44096348-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.-31+496T>G		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.-31+496T>G		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 106253 AN: 150574 Hom.: 37705 Cov.: 28

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.712

GnomAD3 exomes AF: 0.751 AC: 101402 AN: 134962 Hom.: 38648 AF XY: 0.748 AC XY: 54782 AN XY: 73282

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.849

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.923

Gnomad SAS exome AF: 0.730

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.710

Gnomad OTH exome AF: 0.735

GnomAD4 exome AF: 0.719 AC: 992320 AN: 1380666 Hom.: 358250 Cov.: 34 AF XY: 0.719 AC XY: 489668 AN XY: 681166

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.844

Gnomad4 ASJ exome AF: 0.685

Gnomad4 EAS exome AF: 0.904

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.773

Gnomad4 NFE exome AF: 0.710

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.706 AC: 106352 AN: 150692 Hom.: 37746 Cov.: 28 AF XY: 0.713 AC XY: 52456 AN XY: 73610

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.714

Alfa AF: 0.662 Hom.: 4056

Bravo AF: 0.701

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.1
Dann	Benign	0.52

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: rs11037860; hg19: chr11-44117898;