rs137966643
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015374.3(SUN2):āc.166G>Cā(p.Ala56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000756 in 1,613,954 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A56V) has been classified as Uncertain significance.
Frequency
Consequence
NM_015374.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.166G>C | p.Ala56Pro | missense_variant | 3/18 | ENST00000689035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN2 | ENST00000689035.1 | c.166G>C | p.Ala56Pro | missense_variant | 3/18 | NM_015374.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000462 AC: 116AN: 251208Hom.: 0 AF XY: 0.000479 AC XY: 65AN XY: 135798
GnomAD4 exome AF: 0.000795 AC: 1162AN: 1461762Hom.: 2 Cov.: 32 AF XY: 0.000762 AC XY: 554AN XY: 727176
GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24AN XY: 74348
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 56 of the SUN2 protein (p.Ala56Pro). This variant is present in population databases (rs137966643, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SUN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 530819). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SUN2 function (PMID: 25210889). 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