rs368280765
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_032806.6(POMGNT2):c.650G>A(p.Arg217Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R217W) has been classified as Uncertain significance.
Frequency
Consequence
NM_032806.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMGNT2 | NM_032806.6 | c.650G>A | p.Arg217Gln | missense_variant | 2/2 | ENST00000344697.3 | |
POMGNT2 | XM_005265515.4 | c.650G>A | p.Arg217Gln | missense_variant | 3/3 | ||
POMGNT2 | XM_011534163.3 | c.650G>A | p.Arg217Gln | missense_variant | 3/3 | ||
POMGNT2 | XM_017007353.2 | c.650G>A | p.Arg217Gln | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT2 | ENST00000344697.3 | c.650G>A | p.Arg217Gln | missense_variant | 2/2 | 1 | NM_032806.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250662Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135662
GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461736Hom.: 0 Cov.: 37 AF XY: 0.0000413 AC XY: 30AN XY: 727168
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74336
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 217 of the POMGNT2 protein (p.Arg217Gln). This variant is present in population databases (rs368280765, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 449180). 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 POMGNT2 protein function with a negative predictive value of 80%. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 09, 2018 | A variant of uncertain significance has been identified in the POMGNT2 gene. The R217Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R217Q variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in an external variant database. The R217Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species; however, Glutamine is observed at this position in evolution. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at