14 Matching Annotations
  1. Oct 2024
  2. www.sciencedirect.com www.sciencedirect.com
    A noncanonical splicing variant c.875-5 T > G in von Willebrand factor causes in-frame exon skipping and type 2A von Willebrand disease
    1
    1. krisBussey97 14 Oct 2024

      Disease: Von Willebrand Disease (VWD) Type 2A

      Patient: 31 yo, Female

      Variant1: VWF NC_000012.12: c.875-5T>Gdel, p.(Ser292_Glu333delinsLys) Causes complete exon 8 skipping

      Variant2: VWF NM_000552.5: c.813C>G, p.(Tyr271*)

      Phenotypes: History of bleeding (epistaxis, uncontrollable by conventional hemostatic treatment), Easy bruising, gum bleeding, excessive menstrual bleeding, mild decrease in plasma VWF:Ag, severe impairment in VWF function, VWF:Ab/VWF:Ag ratio decreased, VWF:CB/VWF:Ag ratio decreased, FVIII:C lvs slighly below normal range

      Family: Son had bleeding diathesis and spontaneous epistaxis (less severe than proband), normal parents

      In silico data available: SpliceAI delta score of 0.51 for loss of splice acceptor caused by variant 1

      Alamut showed small to moderate effects of the variant on normal splicing of VWF

      NetGene2 showed weak strength of 3' splice sites in exon 8

      SpliceAid2 showed TIA-1 and TIAL 1, which bind to U-rich motifs and facilitate 5' splice site recognition where destroyed in the mutated sequence

      splice variant Ser292_Glu333delinsLys epistaxis uncontrolled by conventional hemostatic treatment excessive menstrual bleeding exon 8 skipping intronic exon 7 variant
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    sciencedirect.com/science/article/pii/S0049384824000379
  3. Mar 2021
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Functional characterization of 84 PALB2 variants of uncertain significance
    2
    1. shannon_mcnulty 18 Mar 2021
      Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).

      AssayResult: 4.1

      AssayResultAssertion: Indeterminate

      StandardErrorMean: 0.56

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:7 CAID:CA288386 ClinVarID:126590
    2. shannon_mcnulty 18 Mar 2021
      A total of 84 PALB2 patient-derived missense variants reported in ClinVar, COSMIC, and the PALB2 LOVD database were selected

      HGVS: NM_024675.3:c.110G>A p.(Arg37His)

      CGType:Variant CG:BulkAnnotation Variant:7 ClinVarID:126590 CAID:CA288386
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    ncbi.nlm.nih.gov/pmc/articles/PMC7056643/
  5. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor
    2
    1. shannon_mcnulty 18 Mar 2021
      SUPPLEMENTARY DATA

      AssayResult: 92.03

      AssayResultAssertion: Not reported

      PValue: > 0.9999

      Comment: Exact values reported in Table S3.

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:7 CAID:CA288441 ClinVarID:126647
    2. shannon_mcnulty 18 Mar 2021
      To this end, 44 missense variants found in breast cancer patients were identified in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar) and/or selected by literature curation based on their frequency of description or amino acid substitution position in the protein (Supplemental Table S1).

      HGVS: NM_024675.3:c.232G>A p.(Val78Ile)

      CGType:Variant CG:BulkAnnotation Variant:7 ClinVarID:126647 CAID:CA288441
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    ncbi.nlm.nih.gov/pmc/articles/PMC6847799/
  6. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2
    4
    1. shannon_mcnulty 18 Mar 2021
      Source Data

      AssayResult: 89.72

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 7.95

      Comment: Exact values reported in “Source Data” file.

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:3 Variant:7 CAID:CA395139401
    2. shannon_mcnulty 18 Mar 2021
      Source Data

      AssayResult: 94.84

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardErrorMean: 20.56

      Comment: Exact values reported in “Source Data” file.

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:2 Variant:7 CAID:CA395139401
    3. shannon_mcnulty 18 Mar 2021
      Source Data

      AssayResult: 105.41

      AssayResultAssertion: Not reported

      ReplicateCount: 2

      StandardDeviation: 9.45

      StandardErrorMean: 6.68

      Comment: Exact values reported in “Source Data” file.

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:7 CAID:CA395139401
    4. shannon_mcnulty 18 Mar 2021
      We, therefore, analyzed the effect of 48 PALB2 VUS (Fig. 2a, blue) and one synthetic missense variant (p.A1025R) (Fig. 2a, purple)29 on PALB2 function in HR.

      HGVS: NM_024675.3:c.124G>A p.(E42K)

      CGType:Variant CG:BulkAnnotation Variant:7 CAID:CA395139401
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    ncbi.nlm.nih.gov/pmc/articles/PMC6876638/
  7. www.cell.com www.cell.com
    High-Throughput Reclassification of SCN5A Variants
    2
    1. shannon_mcnulty 18 Mar 2021
      Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function

      AssayResult: 3.4

      AssayResultAssertion: Abnormal

      ReplicateCount: 22

      StandardErrorMean: 0.8

      Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)

      CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:7 CAID:CA014336 ClinVarID:67635
    2. shannon_mcnulty 18 Mar 2021
      we selected 73 previously unstudied variants: 63 suspected Brugada syndrome variants and 10 suspected benign variants

      HGVS: NM_198056.2:c.1106T>A p.(Met369Lys)

      CGType:Variant CG:BulkAnnotation Variant:7 ClinVarID:67635 CAID:CA014336
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    cell.com/ajhg/fulltext/S0002-9297(20)30162-2
  8. Feb 2021
  9. jmg.bmj.com jmg.bmj.com
    Blood functional assay for rapid clinical interpretation of germline TP53 variants
    3
    1. shannon_mcnulty 24 Feb 2021
      Supplemental material

      AssayResult: 101, 106

      AssayResultAssertion: Normal

      Comment: See Table S3 for details

      CGType:FunctionalAssayResult FuncAssay:4 Variant:7 CAID:CA397832246 ClinVarID:481148
    2. shannon_mcnulty 24 Feb 2021
      Supplemental material

      AssayResult: 4, 5

      AssayResultAssertion: Abnormal

      Comment: See Table S3 for details

      CGType:FunctionalAssayResult FuncAssay:3 Variant:7 CAID:CA397832246 ClinVarID:481148
    3. shannon_mcnulty 24 Feb 2021
      We analysed a total of 82 blood samples derived from 77 individuals (online supplemental table 3). These 77 individuals corresponded either to new index cases suspected to harbour a pathogenic TP53 variant or to relatives of index cases harbouring TP53 variants.

      HGVS: NM_000546.5:c.1054G>T p.(Asp352Tyr)

      CGType:Variant Variant:7 ClinVarID:481148 CAID:CA397832246
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    jmg.bmj.com/content/early/2020/10/13/jmedgenet-2020-107059