8-31087860-AAAG-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000553.6(WRN):c.1530_1532del(p.Glu510del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,605,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. K506K) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 inframe_deletion
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.1530_1532del | p.Glu510del | inframe_deletion | 12/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1530_1532del | p.Glu510del | inframe_deletion | 12/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.231_233del | non_coding_transcript_exon_variant | 1/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1144_*1146del | 3_prime_UTR_variant, NMD_transcript_variant | 11/34 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152016Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000146 AC: 212AN: 1453082Hom.: 0 AF XY: 0.000159 AC XY: 115AN XY: 722790
GnomAD4 genome AF: 0.000184 AC: 28AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74380
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2022 | This variant, c.1530_1532del, results in the deletion of 1 amino acid(s) of the WRN protein (p.Glu510del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 194004). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 18, 2014 | - - |
WRN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 29, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at