14-64202952-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_182914.3(SYNE2):c.18190G>A(p.Ala6064Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,614,140 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6064S) has been classified as Uncertain significance.
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.18190G>A | p.Ala6064Thr | missense_variant | 100/116 | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.18190G>A | p.Ala6064Thr | missense_variant | 100/116 | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000421 AC: 64AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000274 AC: 69AN: 251414Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135890
GnomAD4 exome AF: 0.000236 AC: 345AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.000230 AC XY: 167AN XY: 727218
GnomAD4 genome AF: 0.000420 AC: 64AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74490
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 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 | Dec 19, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 25, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | SYNE2: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at