rs758819862
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000553.6(WRN):c.2518G>A(p.Gly840Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,612,812 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 (★). Synonymous variant affecting the same amino acid position (i.e. G840G) has been classified as Benign.
Frequency
Consequence
NM_000553.6 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 |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2518G>A | p.Gly840Ser | missense_variant | 21/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2518G>A | p.Gly840Ser | missense_variant | 21/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.1151G>A | non_coding_transcript_exon_variant | 9/23 | 1 | ||||
WRN | ENST00000520169.1 | n.357G>A | non_coding_transcript_exon_variant | 1/3 | 3 | ||||
WRN | ENST00000650667.1 | c.*2132G>A | 3_prime_UTR_variant, NMD_transcript_variant | 20/34 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151836Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251148Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135730
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460976Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726778
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 151836Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10AN XY: 74166
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 840 of the WRN protein (p.Gly840Ser). This variant is present in population databases (rs758819862, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 458419). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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