rs756050193
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000553.6(WRN):āc.613C>Gā(p.Leu205Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L205L) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.613C>G | p.Leu205Val | missense_variant | 6/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.613C>G | p.Leu205Val | missense_variant | 6/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000650667.1 | c.*227C>G | 3_prime_UTR_variant, NMD_transcript_variant | 5/34 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251290Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135840
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461616Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727122
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 205 of the WRN protein (p.Leu205Val). This variant is present in population databases (rs756050193, gnomAD 0.003%). This missense change has been observed in individual(s) with a lipid disorder (PMID: 32041611). ClinVar contains an entry for this variant (Variation ID: 458492). 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. 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