chr22-38736343-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015374.3(SUN2):c.2078G>A(p.Arg693Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R693L) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.2078G>A | p.Arg693Gln | missense_variant | 18/18 | ENST00000689035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN2 | ENST00000689035.1 | c.2078G>A | p.Arg693Gln | missense_variant | 18/18 | NM_015374.3 | P2 | ||
ENST00000418803.1 | n.85+1529C>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
ENST00000420118.1 | n.317+1302C>T | 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: 0.0000221 AC XY: 3AN XY: 135602
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461642Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727116
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74330
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 0.008%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 693 of the SUN2 protein (p.Arg693Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at