rs545142847
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBP6_Very_Strong
The ENST00000634267.2(DNM1):c.2545G>A(p.Gly849Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000858 in 1,595,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G849E) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000634267.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000634267.2 | c.2545G>A | p.Gly849Arg | missense_variant | Exon 22 of 22 | 5 | ENSP00000489096.1 | |||
DNM1 | ENST00000372923.8 | c.2541G>A | p.Ser847Ser | synonymous_variant | Exon 22 of 22 | 1 | NM_004408.4 | ENSP00000362014.4 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 151856Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000278 AC: 65AN: 233556Hom.: 0 AF XY: 0.000218 AC XY: 28AN XY: 128280
GnomAD4 exome AF: 0.0000796 AC: 115AN: 1444024Hom.: 0 Cov.: 32 AF XY: 0.0000723 AC XY: 52AN XY: 718750
GnomAD4 genome AF: 0.000145 AC: 22AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74262
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 31A Benign:1
- -
not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
DNM1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at