rs747026081
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000553.6(WRN):c.2029G>A(p.Gly677Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,613,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. G677G) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2029G>A | p.Gly677Arg | missense_variant | 18/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2029G>A | p.Gly677Arg | missense_variant | 18/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.662G>A | non_coding_transcript_exon_variant | 6/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1643G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251432Hom.: 1 AF XY: 0.000110 AC XY: 15AN XY: 135888
GnomAD4 exome AF: 0.000170 AC: 248AN: 1461814Hom.: 1 Cov.: 33 AF XY: 0.000158 AC XY: 115AN XY: 727194
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74266
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 677 of the WRN protein (p.Gly677Arg). This variant is present in population databases (rs747026081, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 238133). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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