rs1383589957
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000553.6(WRN):c.2103_2104del(p.Leu702TyrfsTer29) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000372 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. A701A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000553.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2103_2104del | p.Leu702TyrfsTer29 | frameshift_variant | 19/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2103_2104del | p.Leu702TyrfsTer29 | frameshift_variant | 19/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.736_737del | non_coding_transcript_exon_variant | 7/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1717_*1718del | 3_prime_UTR_variant, NMD_transcript_variant | 18/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251364Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461690Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727152
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Werner syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 15, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change creates a premature translational stop signal (p.Leu702Tyrfs*29) in the WRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Werner syndrome (PMID: 15888165). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 2334delAC. ClinVar contains an entry for this variant (Variation ID: 458404). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at