Back
LYFE SCIENCES
Project: HERA
NM_024675.3:c.1794G>A
p.Leu598=  ·  PALB2
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The PALB2 c.1794G>A (p.Leu598=) variant has been reported in ClinVar with an expert panel Likely Benign classification and additional benign or likely benign clinical laboratory submissions.

clinvar ↗ cspec ↗
2

In gnomAD v4.1, this variant is present at 47/1614132 alleles (0.00291%) with a grpmax filtering allele frequency of 0.04713%, which is above the PALB2 BS1 threshold of 0.01%; gnomAD v2.1 also shows the variant in population databases, including African/African American individuals.

gnomad_v4 ↗ gnomad_v2 ↗ cspec ↗
3

SpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.06, which is below the PALB2 BP4 threshold of 0.1 and below the PP3 threshold of 0.2.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 7.07454e-05; MAF= 0.00707%, 20/282704 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000801218; MAF= 0.08012%, 20/24962 alleles, homozygotes = 0); grpmax FAF= 0.00056887.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 2.91178e-05; MAF= 0.00291%, 47/1614132 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000612925; MAF= 0.06129%, 46/75050 alleles, homozygotes = 0); grpmax FAF= 0.00047131.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Benign (3 clinical laboratories) and as Likely Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueL598
Hotspots ↗