11-44100533-G-T

Position:

• chr11-44100533-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207122.2(EXT2):​c.-31+4681G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,874 control chromosomes in the GnomAD database, including 12,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12575 hom., cov: 31)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.-31+4681G>T		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.-31+4681G>T		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60772 AN: 151756 Hom.: 12556 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60836 AN: 151874 Hom.: 12575 Cov.: 31 AF XY: 0.403 AC XY: 29893 AN XY: 74236

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.376

Alfa AF: 0.337 Hom.: 2509

Bravo AF: 0.395

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.47

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: rs4755227; hg19: chr11-44122083;