chr22-38742380-G-A
Variant summary
Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A330P) has been classified as Uncertain significance.
Frequency
Consequence
NM_015374.3 missense
Scores
Clinical Significance
Conservation
Publications
- neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1Inheritance: AR Classification: MODERATE Submitted by: G2P
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.989C>T | p.Ala330Val | missense_variant | Exon 9 of 18 | ENST00000689035.1 | NP_056189.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000279 AC: 7AN: 250544 AF XY: 0.0000295 show subpopulations
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460992Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726794 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74444 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
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. 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. 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. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at