--- title: "PALB2 C396Lfs*5 (c.1186dup, rs1555461413) | Dante Labs" description: "ClinVar classifies PALB2 C396Lfs*5 as Pathogenic (criteria provided, multiple submitters, no conflicts). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/palb2/variants/c396lfs5" --- 1. [Genes](https://dantelabs.com/genes) 2. [PALB2](https://dantelabs.com/genes/palb2) 3. PALB2 C396Lfs\*5 Variant # PALB2 C396Lfs\*5 NM_024675.4(PALB2):c.1186dup (p.Cys396LeufsTer5) Also known as - p.Cys396LeufsTer5 - p.C396Lfs\*5 - rs1555461413 * ClinVar classification Pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 13 December 2025 Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911 Facts last changed 18 October 2026 ## Summary C396Lfs\*5 is a frameshift variant in PALB2: it adds or removes DNA letters in a way that shifts how the rest of the gene's code is read. ClinVar classifies it as pathogenic for Hereditary breast cancer (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------- | --------------------------------------------------------------------- | ------------- | ---------------- | | [Hereditary breast cancer](https://dantelabs.com/conditions/moderate-penetrance-breast-ovarian-cancer-genes) [ClinVar VCV000402291 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/402291/) | Pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 13 December 2025 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria C396Lfs\*5 meets, from its predicted effect in PALB2, gnomAD and ClinVar. | Criterion | Strength | Rests on | | ------------------------------------------------------- | ----------- | -------------------------------------------------------------------------- | | PVS1 Null variant where loss of function causes disease | Very strong | frameshift_variant on NM_024675.4 | | PM2 Absent or very rare in population databases | Supporting | Not seen in gnomAD exomes, gnomAD genomes | | PP5 A reputable source reports it as pathogenic | Supporting | ClinVar: Pathogenic (criteria provided, multiple submitters, no conflicts) | On these criteria alone: pathogenic. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often C396Lfs\*5 is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | ---------------- | ------------ | ----------- | ------------ | | gnomAD exomes | Not seen | 0 of 0 | 0 | | | gnomAD genomes | Not seen | 0 of 0 | 0 | | Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result. [C396Lfs\*5 in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/16-23635359-C-CA?dataset=gnomad_r4) ## Where it lies in PALB2 C396Lfs\*5 lies in exon 4 of the 13 in PALB2's MANE Select transcript, NM_024675.4. [PALB2 variants in exon 4 →](https://dantelabs.com/genes/palb2/variants?exon=4) [PALB2's gene diagram →](https://dantelabs.com/genes/palb2#gene-structure) ## Molecular details | Gene | [PALB2](https://dantelabs.com/genes/palb2) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_024675.4 MANE Select | | Coding DNA change (HGVS c.) | c.1186dup | | Protein change (HGVS p.) | p.Cys396LeufsTer5 p.C396Lfs\*5 | | Predicted consequence | Frameshift [frameshift_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001589) [frameshift_truncation (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001910) | | Predicted impact | High | | Position (GRCh38) | chr16:23635359 C>CA | | Position (GRCh37) | chr16:23646680 C>CA | | dbSNP ID | [rs1555461413 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1555461413) | | ClinVar Variation ID | [VCV000402291 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/402291/) | | ClinVar Allele ID | 389274 | | ClinGen Allele Registry ID | [CA16609599 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA16609599) | | ClinVar name | NM_024675.4(PALB2):c.1186dup (p.Cys396fs) | ## PALB2 C396Lfs\*5 in other databases - [ClinVar VCV000402291 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/402291/) - [dbSNP rs1555461413 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1555461413) - [ClinGen Allele Registry CA16609599 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA16609599) - [gnomAD 16-23635359-C-CA (opens in a new tab)](https://gnomad.broadinstitute.org/variant/16-23635359-C-CA?dataset=gnomad_r4) - [Ensembl rs1555461413 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs1555461413) ## Reports that look at this variant (1) These Genome Test condition reports include C396Lfs\*5 among the variants they look at. | Report | Conditions | Inheritance | | ---------------------------------------------------------------------------------------------------------------------------------- | ------------------------ | ------------------ | | [Breast and Ovarian Cancer Genes Beyond BRCA1/2](https://dantelabs.com/conditions/moderate-penetrance-breast-ovarian-cancer-genes) | Hereditary breast cancer | Autosomal dominant | ## Other variants in PALB2 - [A842Sfs\*7 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/a842sfs7) - [c.108+1_108+2insC Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/c-108plus1to108plus2insc) - [c.2559C>T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/c-2559c-t) - [c.3350+4A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/c-3350plus4a-g) - [c.3549C>A Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/c-3549c-a) - [E3X Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/e3x) - [E178Nfs\*15 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/e178nfs15) - [G1121Vfs\*3 Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/g1121vfs3) - [L531Cfs\*30 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/l531cfs30) - [N280Tfs\*8 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/palb2/variants/n280tfs8) [All PALB2 variants](https://dantelabs.com/genes/palb2/variants) ## Limitations This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant. Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports. Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements. If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor. ## Sources & credits - Classifications from ClinVar (release 2026-10-12), National Center for Biotechnology Information. - Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0. - Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16). - Allele identifiers from the ClinGen Allele Registry (release 2026-10-19-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-19). - Difficult regions from the Genome in a Bottle Consortium (release v3.6). - Transcripts from MANE (release v1.5), NCBI and EMBL-EBI. - Predicted consequences from mehari (release 0.11.0), with transcript models from cdot. - Built from Dante Labs data release 2026.10.19-9814e911 of 19 October 2026. ## Cite this page APA > Dante Labs. (18 October 2026). PALB2 C396Lfs\*5 (c.1186dup, rs1555461413) (Version 2026.10.19-9814e911). Retrieved 20 October 2026, from https\://dantelabs.com/genes/palb2/variants/c396lfs5 Vancouver > Dante Labs. PALB2 C396Lfs\*5 (c.1186dup, rs1555461413) \[Internet]. Version 2026.10.19-9814e911. 18 October 2026 \[cited 20 October 2026]. Available from: https\://dantelabs.com/genes/palb2/variants/c396lfs5 Download citation [RIS](https://dantelabs.com/genes/palb2/variants/c396lfs5/cite.ris) [BibTeX](https://dantelabs.com/genes/palb2/variants/c396lfs5/cite.bib) [CSL-JSON](https://dantelabs.com/genes/palb2/variants/c396lfs5/cite.json) ## Read your whole genome From $449 Free shipping · Results in 6–8 weeks [Explore the Genome Test](https://dantelabs.com/whole-genome-sequencing)