chr11-44197916-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PVS1PP5BS2
The NM_207122.2(EXT2):c.1393C>T(p.Arg465Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_207122.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXT2 | NM_207122.2 | c.1393C>T | p.Arg465Ter | stop_gained | 9/14 | ENST00000533608.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT2 | ENST00000533608.7 | c.1393C>T | p.Arg465Ter | stop_gained | 9/14 | 1 | NM_207122.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251356Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135830
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727190
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74448
ClinVar
Submissions by phenotype
Exostoses, multiple, type 2 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2023 | This variant has not been reported in the literature in individuals affected with EXT2-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 580003). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg465*) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 06, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 05, 2019 | The EXT2 c.1393C>T (p.Arg465Ter) variant variant is a stop-gained variant, which was observed 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for hereditary multiple osteochondromatosis. - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 20, 2023 | - - |
Exostoses, multiple, type 2;C4225248:Seizures-scoliosis-macrocephaly syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at