rs117647282
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182914.3(SYNE2):c.4178G>A(p.Arg1393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,614,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1393W) has been classified as Benign.
Frequency
Consequence
NM_182914.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.4178G>A | p.Arg1393Gln | missense_variant | 30/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.4178G>A | p.Arg1393Gln | missense_variant | 30/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000611 AC: 93AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000463 AC: 115AN: 248532Hom.: 1 AF XY: 0.000482 AC XY: 65AN XY: 134862
GnomAD4 exome AF: 0.000726 AC: 1061AN: 1461816Hom.: 2 Cov.: 33 AF XY: 0.000681 AC XY: 495AN XY: 727212
GnomAD4 genome ? AF: 0.000611 AC: 93AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 17, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 26, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | - - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 02, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | 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. - |
SYNE2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 02, 2023 | 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