NM_182914.3:c.17539G>A
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182914.3(SYNE2):c.17539G>A(p.Glu5847Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. E5847Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_182914.3 missense
Scores
Clinical Significance
Conservation
Publications
- male infertility with azoospermia or oligozoospermia due to single gene mutationInheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
- familial medullary thyroid carcinomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- ovarian dysgenesis 8Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.17539G>A | p.Glu5847Lys | missense_variant | Exon 96 of 116 | ENST00000555002.6 | NP_878918.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.17539G>A | p.Glu5847Lys | missense_variant | Exon 96 of 116 | 1 | NM_182914.3 | ENSP00000450831.2 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152140Hom.: 1 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000477 AC: 12AN: 251324 AF XY: 0.0000515 show subpopulations
GnomAD4 exome AF: 0.000154 AC: 225AN: 1461772Hom.: 1 Cov.: 32 AF XY: 0.000143 AC XY: 104AN XY: 727178 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000151 AC: 23AN: 152258Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74460 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:2Benign:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 5847 of the SYNE2 protein (p.Glu5847Lys). This variant is present in population databases (rs201427580, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 283208). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -
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. -
- -
not provided Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at