rs45590135
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182914.3(SYNE2):āc.7163A>Gā(p.Glu2388Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,614,190 control chromosomes in the GnomAD database, including 10 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. E2388K) has been classified as Likely benign.
Frequency
Consequence
NM_182914.3 missense
Scores
Clinical Significance
Conservation
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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.7163A>G | p.Glu2388Gly | missense_variant | 45/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.7163A>G | p.Glu2388Gly | missense_variant | 45/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 186AN: 152250Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.00168 AC: 419AN: 248780Hom.: 1 AF XY: 0.00184 AC XY: 248AN XY: 135080
GnomAD4 exome AF: 0.00187 AC: 2732AN: 1461822Hom.: 9 Cov.: 64 AF XY: 0.00192 AC XY: 1394AN XY: 727204
GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152368Hom.: 1 Cov.: 34 AF XY: 0.00106 AC XY: 79AN XY: 74510
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.7163A>G (p.E2388G) alteration is located in exon 45 (coding exon 44) of the SYNE2 gene. This alteration results from a A to G substitution at nucleotide position 7163, causing the glutamic acid (E) at amino acid position 2388 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Sep 18, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 13, 2015 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 06, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | SYNE2: BS1, BS2 - |
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:2
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 | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at