rs143904314
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM1PP2BP4_StrongBS2_Supporting
The ENST00000261405.10(VWF):āc.2340C>Gā(p.Asn780Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
ENST00000261405.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.2340C>G | p.Asn780Lys | missense_variant | 18/52 | ENST00000261405.10 | NP_000543.3 | |
VWF | XM_047429501.1 | c.2340C>G | p.Asn780Lys | missense_variant | 18/52 | XP_047285457.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.2340C>G | p.Asn780Lys | missense_variant | 18/52 | 1 | NM_000552.5 | ENSP00000261405 | P1 | |
VWF | ENST00000538635.5 | n.421-50459C>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000664 AC: 101AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251352Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135860
GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461890Hom.: 0 Cov.: 35 AF XY: 0.0000688 AC XY: 50AN XY: 727246
GnomAD4 genome AF: 0.000670 AC: 102AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000523 AC XY: 39AN XY: 74500
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 20, 2023 | Variant summary: VWF c.2340C>G (p.Asn780Lys) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 251352 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2340C>G in individuals affected with Von Willebrand Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 19, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 16, 2023 | In the published literature, this variant has been reported in healthy individuals (PMIDs: 3342085 (2020), 23690449 (2013)). The frequency of this variant in the general population, 0.003 (75/24960 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. - |
VWF-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 29, 2024 | The VWF c.2340C>G variant is predicted to result in the amino acid substitution p.Asn780Lys. To our knowledge, this variant has not been reported in VWF related disease. This variant is reported in 0.30% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at