rs755548890
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000298139.7(WRN):āc.1504G>Cā(p.Gly502Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,613,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G502V) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000298139.7 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 |
---|---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.1504G>C | p.Gly502Arg | missense_variant | 12/35 | ENST00000298139.7 | NP_000544.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1504G>C | p.Gly502Arg | missense_variant | 12/35 | 1 | NM_000553.6 | ENSP00000298139 | P1 | |
WRN | ENST00000521620.5 | n.205G>C | non_coding_transcript_exon_variant | 1/23 | 1 | |||||
WRN | ENST00000650667.1 | c.*1118G>C | 3_prime_UTR_variant, NMD_transcript_variant | 11/34 | ENSP00000498593 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250880Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135566
GnomAD4 exome AF: 0.0000917 AC: 134AN: 1461458Hom.: 0 Cov.: 30 AF XY: 0.0000894 AC XY: 65AN XY: 727028
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74294
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 502 of the WRN protein (p.Gly502Arg). This variant is present in population databases (rs755548890, gnomAD 0.008%). 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: 528181). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 13, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at