chr11-44114298-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_207122.2(EXT2):c.740C>G(p.Pro247Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P247Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_207122.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXT2 | NM_207122.2 | c.740C>G | p.Pro247Arg | missense_variant | 4/14 | ENST00000533608.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXT2 | ENST00000533608.7 | c.740C>G | p.Pro247Arg | missense_variant | 4/14 | 1 | NM_207122.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251360Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135842
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460364Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726634
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Exostoses, multiple, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EXT2 protein function. ClinVar contains an entry for this variant (Variation ID: 1040250). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. This variant is present in population databases (rs372237191, gnomAD 0.03%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 247 of the EXT2 protein (p.Pro247Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at