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.2014G>C
Protein Change
E672Q
Location
Exon 5 (Exon 5 of )
5
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
2.24 in 100,000
Extremely Rare
ACMG Criteria Applied BA1

ClinVar

Open
Classification
Likely Benign
2 publications
Publications List
PMID: 17200668

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Marc Tischkowitz, Maximiliano Zeballos, Melissa DeRycke.

Clinical Statement

"This variant has been reported in ClinVar as Benign (22 clinical laboratories) and as Likely benign (4 clinical laboratories) and as Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM4986920
Recurrence
30 occurrences
PM1 Criteria
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: PALB2E672QPALB2E672QSomaticNCBI Gene:79728|Show additional gene information Variant OverviewPALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.The PALB2 E672Q mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: PALB2 E672Q does not lie within any known functional domains of the Palb2 protein (UniProt.org). E672Q results in homology-directed DNA repair activity similar to wild-type Palb2 in a reporter assay (PMID: 33964450), and homology-directed DNA repair activity similar to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951).

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) 0.01 190 bp
- Donor Loss (DL) 0.0 136 bp
+ Acceptor Gain (AG) 0.0 232 bp
+ Donor Gain (DG) 0.0 -180 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:
BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP6

BP6 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)