rs903509

Variant names:

• chr11-44241259-G-A
• rs903509
• NM_207122.2:c.2019-2890G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-44241259-G-A
• chr11-44241259-G-C
• chr11-44241259-G-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.2019-2890G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,220 control chromosomes in the GnomAD database, including 61,943 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 0.90 (61943 hom., cov: 31)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, G2P
• seizures-scoliosis-macrocephaly syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.2019-2890G>A		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.2118-2890G>A		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.2049-2890G>A		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.2019-2890G>A		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.2049-2890G>A		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.2019-2890G>A		intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137129 AN: 152102 Hom.: 61896 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.902 AC: 137235 AN: 152220 Hom.: 61943 Cov.: 31 AF XY: 0.903 AC XY: 67174 AN XY: 74428

African (AFR) AF: 0.878 AC: 36456 AN: 41506

American (AMR) AF: 0.941 AC: 14402 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3111 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5130 AN: 5182

South Asian (SAS) AF: 0.865 AC: 4157 AN: 4808

European-Finnish (FIN) AF: 0.912 AC: 9676 AN: 10606

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61222 AN: 68028

Other (OTH) AF: 0.913 AC: 1924 AN: 2108

Alfa AF: 0.894 Hom.: 5943

Bravo AF: 0.906

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs903509;

hg19: chr11-44262809;