rs564884199
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015374.3(SUN2):c.989C>T(p.Ala330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015374.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.989C>T | p.Ala330Val | missense_variant | 9/18 | ENST00000689035.1 | NP_056189.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SUN2 | ENST00000689035.1 | c.989C>T | p.Ala330Val | missense_variant | 9/18 | NM_015374.3 | ENSP00000508608 | P2 | ||
ENST00000416406.1 | n.165+3213G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250544Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135674
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460992Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726794
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74444
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 08, 2019 | This sequence change replaces alanine with valine at codon 330 of the SUN2 protein (p.Ala330Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs564884199, ExAC 0.006%) but has not been reported in the literature in individuals with a SUN2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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