rs748169173
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000553.6(WRN):c.2521G>A(p.Ala841Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,612,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A841P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000553.6 missense
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.2521G>A | p.Ala841Thr | missense_variant | 21/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2521G>A | p.Ala841Thr | missense_variant | 21/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.1154G>A | non_coding_transcript_exon_variant | 9/23 | 1 | ||||
WRN | ENST00000520169.1 | n.360G>A | non_coding_transcript_exon_variant | 1/3 | 3 | ||||
WRN | ENST00000650667.1 | c.*2135G>A | 3_prime_UTR_variant, NMD_transcript_variant | 20/34 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 151904Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251160Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135734
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1460990Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 726794
GnomAD4 genome AF: 0.0000592 AC: 9AN: 151904Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6AN XY: 74190
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 22, 2021 | The c.2521G>A (p.A841T) alteration is located in exon 21 (coding exon 20) of the WRN gene. This alteration results from a G to A substitution at nucleotide position 2521, causing the alanine (A) at amino acid position 841 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 841 of the WRN protein (p.Ala841Thr). This variant is present in population databases (rs748169173, gnomAD 0.02%). 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: 195567). 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: "Possibly 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 03, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at