chr11-44095838-G-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_207122.2(EXT2):c.-45G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 171,300 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 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
EXT2
NM_207122.2 5_prime_UTR
NM_207122.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.35
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXT2 | NM_207122.2 | c.-45G>T | 5_prime_UTR_variant | 1/14 | ENST00000533608.7 | ||
EXT2 | NM_001178083.3 | c.-45G>T | 5_prime_UTR_variant | 1/15 | |||
EXT2 | NM_001389630.1 | c.-84G>T | 5_prime_UTR_variant | 1/15 | |||
EXT2 | XM_047426529.1 | c.-197G>T | 5_prime_UTR_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT2 | ENST00000533608.7 | c.-45G>T | 5_prime_UTR_variant | 1/14 | 1 | NM_207122.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000523 AC: 1AN: 19130Hom.: 0 Cov.: 0 AF XY: 0.000103 AC XY: 1AN XY: 9694
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74328
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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 | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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