11-44241259-G-A

Position:

• chr11-44241259-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.2019-2890G>A		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.2019-2890G>A		intron_variant		1	NM_207122.2	P1

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.913

Alfa AF: 0.895 Hom.: 5640

Bravo AF: 0.906

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs903509; hg19: chr11-44262809;