8-31087860-A-AAAG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.1530_1532dup(p.Glu510dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K506K) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.1530_1532dup | p.Glu510dup | inframe_insertion | 12/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1530_1532dup | p.Glu510dup | inframe_insertion | 12/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.231_233dup | non_coding_transcript_exon_variant | 1/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1144_*1146dup | 3_prime_UTR_variant, NMD_transcript_variant | 11/34 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 248098Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134164
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461220Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726908
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This variant, c.1530_1532dup, results in the insertion of 1 amino acid(s) of the WRN protein (p.Glu510dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.009%). 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: 404028). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at