Genetic Information

Gene & Transcript Details

Gene
PALB2
Transcript
NM_024675.3 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_024675.3:c.2787_2788dup
Protein Change
N930Ifs*6
Location
Exon 8 (Exon 8 of )
8
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
Unknown
0 publications
Clinical Statement

""

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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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: PALB2N930Ifs*6PALB2N930Ifs*6SomaticNCBI Gene:79728|Show additional gene information Variant OverviewPALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.The PALB2 N930Ifs*6 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in PALB2 is: PALB2 truncating mutations can form several forms of C-terminally truncated PALB2 protein and are found in breast cancers. As such, PALB2 is considered a rare breast cancer susceptibility gene. In patient studies, PALB2 truncation mutations were shown to significantly increase the risk of breast cancer, with similar risks for estrogen receptor-positive and -negative breast cancer. PALB2 truncation mutations have also been found in cases of hereditary male breast cancer (PMID: 28858227, 18053174, 25529982, 29484706, 28279176, 28779002). 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
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.14 40 bp
- Donor Loss (DL) 0.2 -45 bp
+ Acceptor Gain (AG) 0.0 -15 bp
+ Donor Gain (DG) 0.0 -114 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:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)