rs1805069
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_006005.3(WFS1):c.1726G>A(p.Gly576Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00462 in 1,613,806 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G576C) has been classified as Uncertain significance.
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.1726G>A | p.Gly576Ser | missense_variant | 8/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.1726G>A | p.Gly576Ser | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.1726G>A | p.Gly576Ser | missense_variant | 8/8 | 1 | NM_006005.3 | P2 | |
ENST00000661896.1 | n.1337+2394C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0110 AC: 1672AN: 152208Hom.: 25 Cov.: 34
GnomAD3 exomes AF: 0.00954 AC: 2397AN: 251166Hom.: 58 AF XY: 0.00806 AC XY: 1095AN XY: 135842
GnomAD4 exome AF: 0.00396 AC: 5789AN: 1461478Hom.: 188 Cov.: 99 AF XY: 0.00374 AC XY: 2721AN XY: 727078
GnomAD4 genome ? AF: 0.0110 AC: 1674AN: 152328Hom.: 25 Cov.: 34 AF XY: 0.0112 AC XY: 837AN XY: 74486
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Gly576Ser in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 1.9% (72/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs1805069). - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 06, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 23, 2015 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
WFS1-Related Spectrum Disorders Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Monogenic diabetes Benign:1
Benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Feb 08, 2019 | ACMG criteria: BA1 (6.7% in gnomAD SA, 2.3% in gnomAD African), BS2 (62 homozygotes in gnomAD)=Benign (REVEL 0.534 + precictor evidence not consistent, not using) - |
Autosomal dominant nonsyndromic hearing loss 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Wolfram syndrome 1 Other:1
Uncertain risk allele, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy.However no sufficient evidence is found to ascertain the role of this particular variant rs1805069 yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at