11-44100533-G-T

Variant names:

• chr11-44100533-G-T
• rs4755227
• NM_207122.2:c.-31+4681G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• exostoses, multiple, type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, Ambry Genetics
• seizures-scoliosis-macrocephaly syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary multiple osteochondromas

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207122.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT2	NM_207122.2	MANE Select	c.-31+4681G>T		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.69+4212G>T		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.-31+4681G>T		intron	N/A	NP_001171554.1	Q93063-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT2	ENST00000533608.7	TSL:1 MANE Select	c.-31+4681G>T		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.-31+4681G>T		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.-31+4212G>T		intron	N/A	ENSP00000342656.3	Q93063-1

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

African (AFR) AF: 0.482 AC: 19943 AN: 41414

American (AMR) AF: 0.321 AC: 4909 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2609 AN: 5142

South Asian (SAS) AF: 0.356 AC: 1712 AN: 4806

European-Finnish (FIN) AF: 0.430 AC: 4535 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24487 AN: 67910

Other (OTH) AF: 0.376 AC: 791 AN: 2104

Alfa AF: 0.339 Hom.: 2594

Bravo AF: 0.395

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.47
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4755227; hg19: chr11-44122083;