Genetic Information

Gene & Transcript Details

Gene
PALB2
Transcript
NM_024675.4 MANE Select
Total Exons
Reference Sequence
NC_000016.9
Alternative Transcripts
IDStatusDetails
NM_024675.4 MANE Select 4008 nt | 154–3714
NM_024675.3 RefSeq Select 4069 nt | 201–3761

Variant Details

HGVS Notation
NM_024675.4:c.1432T>C
Protein Change
S478P
Location
Exon 4 (Exon 4 of )
4
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Uncertain Significance (VUS)
2 publications
Clinical Statement

"This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories) and as Likely benign (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
Accessing full COSMIC database details requires institutional login or subscription.

Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene PALB2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: PALB2S478PPALB2S478PSomaticNCBI Gene:79728|Show additional gene information Variant OverviewPALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.The PALB2 S478P mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 212 bp
- Donor Loss (DL) 0.01 -252 bp
+ Acceptor Gain (AG) 0.0 -191 bp
+ Donor Gain (DG) 0.0 -190 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)