chr11-44096305-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000343631.4(EXT2):c.-47A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,535,810 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
EXT2
ENST00000343631.4 5_prime_UTR
ENST00000343631.4 5_prime_UTR
Scores
15
Clinical Significance
Conservation
PhyloP100: -2.84
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0437645).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXT2 | NM_207122.2 | c.-31+453A>G | intron_variant | ENST00000533608.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT2 | ENST00000533608.7 | c.-31+453A>G | intron_variant | 1 | NM_207122.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000145 AC: 2AN: 1383672Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1AN XY: 682800
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
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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 submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | May 23, 2022 | The EXT2 c.53A>G (p.Gln18Arg) missense change is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). It is predicted to have a benign effect on protein function (BP4), but to our knowledge this prediction has not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with hereditary multiple exostoses. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, BP4. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Vest4
MutPred
Gain of disorder (P = 0.079);
MVP
MPC
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at