chr11-44107732-A-G
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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
NM_207122.2 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 6.99
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 |
---|---|---|---|---|---|---|---|
EXT2 | NM_207122.2 | c.20A>G | p.Tyr7Cys | missense_variant | 2/14 | ENST00000533608.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT2 | ENST00000533608.7 | c.20A>G | p.Tyr7Cys | missense_variant | 2/14 | 1 | NM_207122.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251396Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome Cov.: 32
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32
ExAC
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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 submitter | clinical testing | Baylor Genetics | Jan 12, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;D;D;D;D
Sift4G
Uncertain
T;T;D;D;D;T
Polyphen
B;.;.;P;.;B
Vest4
MutPred
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
MPC
0.76
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at