rs200437377
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000555002.6(SYNE2):c.3506G>A(p.Arg1169His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,613,294 control chromosomes in the GnomAD database, including 1 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. R1169C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000555002.6 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.3506G>A | p.Arg1169His | missense_variant | 28/116 | ENST00000555002.6 | NP_878918.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.3506G>A | p.Arg1169His | missense_variant | 28/116 | 1 | NM_182914.3 | ENSP00000450831 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000533 AC: 81AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000494 AC: 123AN: 249150Hom.: 1 AF XY: 0.000525 AC XY: 71AN XY: 135198
GnomAD4 exome AF: 0.000992 AC: 1450AN: 1461082Hom.: 1 Cov.: 31 AF XY: 0.000985 AC XY: 716AN XY: 726856
GnomAD4 genome AF: 0.000532 AC: 81AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35AN XY: 74412
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 19, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 12, 2023 | - - |
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 25, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.3506G>A (p.R1169H) alteration is located in exon 28 (coding exon 27) of the SYNE2 gene. This alteration results from a G to A substitution at nucleotide position 3506, causing the arginine (R) at amino acid position 1169 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 07, 2015 | - - |
SYNE2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 10, 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