rs771680833
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_182914.3(SYNE2):c.12381+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_182914.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.12381+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000555002.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.12381+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_182914.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461480Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727006
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74430
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 17, 2023 | This sequence change falls in intron 63 of the SYNE2 gene. It does not directly change the encoded amino acid sequence of the SYNE2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs771680833, gnomAD 0.005%). 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: 470921). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at