rs746903992
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP2PP3_Strong
The NM_001005361.3(DNM2):c.1463C>A(p.Thr488Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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. T488R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001005361.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM2 | NM_001005361.3 | c.1463C>A | p.Thr488Lys | missense_variant | 12/21 | ENST00000389253.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM2 | ENST00000389253.9 | c.1463C>A | p.Thr488Lys | missense_variant | 12/21 | 5 | NM_001005361.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251468Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135916
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2021 | The p.T488K variant (also known as c.1463C>A), located in coding exon 12 of the DNM2 gene, results from a C to A substitution at nucleotide position 1463. The threonine at codon 488 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at