Starting
Initialising…
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PALB2
Final classification
Benign
PALB2 c.721A>G · p.Asn241Asp
PALB2

The PALB2 VCEP specification defines BA1 at gnomAD v4 grpmax filtering AF >0.1%, BS1 at >0.01%, and BP1 for all missense variants.

Gene
PALB2
Transcript
NM_024675.4
HGVS · transcript:coding
NM_024675.4:c.721A>G
Consequence
N/A
GRCh38
chr16:23635825 T>C
GRCh37
chr16:23647146 T>C
Basis PALB2 Hereditary Breast, Ovarian and Pancreatic Cancer VCEP v1.2.0 qualitative ACMG/AMP classification
PALB2 Hereditary Breast, Ovarian and Pancreatic Cancer VCEP v1.2.0 qualitative ACMG/AMP classification
Classification rationale
BP1BS1BA1 Benign
PALB2 c.721A>G

The PALB2 VCEP specification defines BA1 at gnomAD v4 grpmax filtering AF >0.1%, BS1 at >0.01%, and BP1 for all missense variants.1 In the assembled workspace, gnomAD v4 reports grpmax_faf 0.00602134 (~0.602%), which exceeds both the BA1 and BS1 PALB2 thresholds by a wide margin.2 The variant is a missense substitution p.(Asn241Asp)/p.(N241D), so PALB2-specific BP1 also applies; ClinVar expert-panel benign classification is concordant but was not needed as an ACMG criterion because BA1 alone is sufficient for a benign call.3

BP1 + BS1 + BA1 Benign
Gene diagram · NM_024675.4 · variants mapped to exon structure
PALB2 NM_024675.4
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      Research & evidence
      Population frequency · supports benign
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      Allele frequency by ancestry
      three datasets · side by side
      ClinVar screenshot
      ClinVar
      This variant has been reported in ClinVar as Benign (9 clinical laboratories) and as Likely benign (8 clinical laboratories) and as Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel).
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
      Functional / OncoKB screenshot
      Functional
      OncoKB classifies this variant as Inconclusive; biological effect: Inconclusive.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence
      COSMIC
      This variant has previously been reported in somatic cancers (COSMIC; COSV104552978, n = 1 times).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      Sources & reference links
      6Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB