chr11-44107732-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207122.2(EXT2):​c.20A>G​(p.Tyr7Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EXT2
NM_207122.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.99
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30374414).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EXT2NM_207122.2 linkuse as main transcriptc.20A>G p.Tyr7Cys missense_variant 2/14 ENST00000533608.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EXT2ENST00000533608.7 linkuse as main transcriptc.20A>G p.Tyr7Cys missense_variant 2/141 NM_207122.2 P1Q93063-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251396
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Exostoses, multiple, type 2 Uncertain:2
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsJan 12, 2024- -
Uncertain significance, criteria provided, single submitterclinical testingInvitaeOct 22, 2023This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 7 of the EXT2 protein (p.Tyr7Cys). This variant is present in population databases (rs765725291, gnomAD 0.006%). 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
0.095
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Benign
0.91
DEOGEN2
Benign
0.41
T;T;.;.;.;T
Eigen
Benign
-0.043
Eigen_PC
Benign
0.043
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.79
.;T;T;T;T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.30
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.97
L;.;.;L;.;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.0
N;D;N;N;N;N
REVEL
Uncertain
0.31
Sift
Uncertain
0.013
D;T;D;D;D;D
Sift4G
Uncertain
0.050
T;T;D;D;D;T
Polyphen
0.42
B;.;.;P;.;B
Vest4
0.72
MutPred
0.30
Loss of MoRF binding (P = 0.0677);Loss of MoRF binding (P = 0.0677);Loss of MoRF binding (P = 0.0677);Loss of MoRF binding (P = 0.0677);.;Loss of MoRF binding (P = 0.0677);
MVP
0.73
MPC
0.76
ClinPred
0.79
D
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.89

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765725291; hg19: chr11-44129282; API