rs538253489
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_001005361.3(DNM2):c.1641C>A(p.Ala547=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A547A) has been classified as Likely benign.
Frequency
Consequence
NM_001005361.3 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM2 | NM_001005361.3 | c.1641C>A | p.Ala547= | synonymous_variant | 15/21 | ENST00000389253.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM2 | ENST00000389253.9 | c.1641C>A | p.Ala547= | synonymous_variant | 15/21 | 5 | NM_001005361.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244302Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132402
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1457756Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 724962
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This sequence change affects codon 547 of the DNM2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNM2 protein. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 465281). This variant has not been reported in the literature in individuals affected with DNM2-related conditions. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at