chr11-44107734-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207122.2(EXT2):​c.22A>G​(p.Asn8Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EXT2
NM_207122.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21394116).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EXT2NM_207122.2 linkuse as main transcriptc.22A>G p.Asn8Asp missense_variant 2/14 ENST00000533608.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EXT2ENST00000533608.7 linkuse as main transcriptc.22A>G p.Asn8Asp missense_variant 2/141 NM_207122.2 P1Q93063-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Exostoses, multiple, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 16, 2023This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 8 of the EXT2 protein (p.Asn8Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.28
T;T;.;.;.;T
Eigen
Benign
-0.087
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
.;D;D;D;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.21
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.;N;.;N
MutationTaster
Benign
0.94
D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.63
N;D;N;N;N;N
REVEL
Benign
0.063
Sift
Benign
0.050
D;D;D;D;D;D
Sift4G
Benign
0.61
T;T;T;T;T;T
Polyphen
0.0060
B;.;.;B;.;B
Vest4
0.39
MutPred
0.30
Loss of MoRF binding (P = 0.0205);Loss of MoRF binding (P = 0.0205);Loss of MoRF binding (P = 0.0205);Loss of MoRF binding (P = 0.0205);.;Loss of MoRF binding (P = 0.0205);
MVP
0.58
MPC
0.28
ClinPred
0.83
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-44129284; API