chr22-38736343-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015374.3(SUN2):c.2078G>T(p.Arg693Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R693Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_015374.3 missense
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 |
---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.2078G>T | p.Arg693Leu | missense_variant | 18/18 | ENST00000689035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN2 | ENST00000689035.1 | c.2078G>T | p.Arg693Leu | missense_variant | 18/18 | NM_015374.3 | P2 | ||
ENST00000418803.1 | n.85+1529C>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
ENST00000420118.1 | n.317+1302C>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250854Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135602
GnomAD4 exome AF: 0.0000828 AC: 121AN: 1461642Hom.: 0 Cov.: 30 AF XY: 0.0000839 AC XY: 61AN XY: 727116
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74458
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SUN2-related conditions. This variant is present in population databases (rs137996727, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 693 of the SUN2 protein (p.Arg693Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at