GeneBe

16-23634974-TGA-ACT

Variant names:
GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.
+1 Uncertain · Cold
-7
-6
-1
0
+5
+6
+9
+10
B
LB
VUS
LP
P
 The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB4_Supporting

The NM_024675.4(PALB2):c.1570_1572delTCAinsAGT (p.525) variant causes a synonymous change. The gene PALB2 is a tumor suppressor gene (CancerMine: 8 TSG, 1 oncogene, 3 driver citations). The gene PALB2 is a known oncogene (CancerMine: 8 TSG, 1 oncogene, 3 driver citations). The gene PALB2 is a cancer driver gene (CancerMine: 8 TSG, 1 oncogene, 3 driver citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PALB2
NM_024675.4 synonymous

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

Publications

0 publications found
Variant links:
Genes affected
PALB2 (HGNC:26144): (partner and localizer of BRCA2) This gene encodes a protein that may function in tumor suppression. This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2. [provided by RefSeq, Jul 2008]
PALB2 Gene-Disease associations (from GenCC):
  • hereditary breast carcinoma
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
  • PALB2-related cancer predisposition
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • Fanconi anemia complementation group N
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
  • pancreatic cancer, susceptibility to, 3
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • Fanconi anemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_024675.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

O3Absent or very rare in population
Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
B4Synonymous/intronic, no splicing impact
Synonymous/intronic variant outside canonical splice sites (B4 supporting); Synonymous variant — splicing impact not confirmed absent; B4 supporting [-1]

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_024675.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

PALB2 NM_024675.4
MANE Select
HGVSc / HGVSpc.1570_1572delTCAinsAGTp.525
Exon rankN/A
synonymous
Prot: NP_078951.2
PALB2 NM_001407296.1
HGVSc / HGVSpc.1510_1512delTCAinsAGTp.505
Exon rankN/A
synonymous
Prot: NP_001394225.1
PALB2 NM_001407297.1
HGVSc / HGVSpc.1570_1572delTCAinsAGTp.525
Exon rankN/A
synonymous
Prot: NP_001394226.1

Ensembl Transcripts

PALB2 ENST00000261584.9
TSL:1MANE Select
HGVSc / HGVSpc.1570_1572delTCAinsAGTp.525
Exon rankN/A
synonymous
Prot: ENSP00000261584.4UniProt: Q86YC2
PALB2 ENST00000568219.5
TSL:1
HGVSc / HGVSpc.685_687delTCAinsAGTp.230
Exon rankN/A
synonymous
Prot: ENSP00000454703.2UniProt: H3BN63
PALB2 ENST00000561514.3
TSL:5
HGVSc / HGVSpc.1576_1578delTCAinsAGTp.527
Exon rankN/A
synonymous
Prot: ENSP00000460666.3UniProt: A0AA52I2C1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)
Rare (AF ≤ 0.0001 / Hom ≤ 1)
Global population databases 2 sources
GnomAD3 genomes
Cov:32
GnomAD4 genome
Cov:32
Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

PhyloP100
Benign0.43
Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

Other links and lift over

hg19: chr16-23646295;
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