chr16-23607914-A-C

Variant names:

• chr16-23607914-A-C
• rs45516100
• NM_024675.4:c.3300T>G
• PALB2 p.Thr1100Thr

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The ENST00000561764.1(PALB2-AS1):n.185+531A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000561764.1 is not a MANE Select or MANE Plus Clinical transcript for PALB2-AS1; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.0277 (AC=44,720) in the gnomAD database across 1,614,080 control chromosomes, including 732 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0558. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). The variant has been observed in cBioPortal in 2 samples across 2 studies and 2 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.).

• Frequency:
  • Genomes: 𝑓 0.025 (72 hom., cov: 31)
  • Exomes 𝑓: 0.028 (660 hom.)
• Consequence: PALB2-AS1 ENST00000561764.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:25
• Conservation: PhyloP100: 0.305
• Publications: 30 publications found

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

PALB2-AS1 (HGNC:58305): ()

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.0558 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000561764.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PALB2 NM_024675.4	MANE Select	c.3300T>G p.Thr1100Thr	synonymous	Exon 12 of 13	Prot: NP_078951.2
	PALB2 NM_001407296.1		c.3240T>G p.Thr1080Thr	synonymous	Exon 11 of 12	Prot: NP_001394225.1
	PALB2 NM_001407297.1		c.3228T>G p.Thr1076Thr	synonymous	Exon 11 of 12	Prot: NP_001394226.1

PALB2 NM_024675.4

MANE Select

HGVSc / HGVSpc.3300T>Gp.Thr1100Thr

Exon rankExon 12 of 13

synonymous

Prot: NP_078951.2

PALB2 NM_001407296.1

HGVSc / HGVSpc.3240T>Gp.Thr1080Thr

Exon rankExon 11 of 12

synonymous

Prot: NP_001394225.1

PALB2 NM_001407297.1

HGVSc / HGVSpc.3228T>Gp.Thr1076Thr

Exon rankExon 11 of 12

synonymous

Prot: NP_001394226.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PALB2 ENST00000261584.9	TSL:1MANE Select	c.3300T>G p.Thr1100Thr	synonymous	Exon 12 of 13	Prot: ENSP00000261584.4 UniProt:
	PALB2 ENST00000568219.5	TSL:1	c.2415T>G p.Thr805Thr	synonymous	Exon 12 of 13	Prot: ENSP00000454703.2 UniProt:
	PALB2 ENST00000561514.3	TSL:5	c.3306T>G p.Thr1102Thr	synonymous	Exon 12 of 13	Prot: ENSP00000460666.3 UniProt:
	PALB2 ENST00000697379.2		c.3306T>G p.Thr1102Thr	synonymous	Exon 13 of 14	Prot: ENSP00000513287.2 UniProt:
	PALB2 ENST00000970391.1		c.3228T>G p.Thr1076Thr	synonymous	Exon 11 of 12	Prot: ENSP00000640450.1 UniProt:
	PALB2 ENST00000697377.2		c.3144T>G p.Thr1048Thr	synonymous	Exon 12 of 13	Prot: ENSP00000513286.2 UniProt:
	PALB2 ENST00000916249.1		c.3138T>G p.Thr1046Thr	synonymous	Exon 11 of 12	Prot: ENSP00000586308.1 UniProt:
	PALB2 ENST00000916250.1		c.3021T>G p.Thr1007Thr	synonymous	Exon 10 of 11	Prot: ENSP00000586309.1 UniProt:
	PALB2 ENST00000697374.1		c.2415T>G p.Thr805Thr	synonymous	Exon 12 of 13	Prot: ENSP00000513284.1 UniProt:
	PALB2 ENST00000697383.1		c.834T>G p.Thr278Thr	synonymous	Exon 8 of 9	Prot: ENSP00000513289.1 UniProt:
	PALB2 ENST00000853528.1		c.147T>G p.Thr49Thr	synonymous	Exon 2 of 3	Prot: ENSP00000523587.1 UniProt:
	PALB2 ENST00000713774.1		c.3114-4245T>G	intron	Intron 10 of 10	Prot: ENSP00000519076.1 UniProt:
	PALB2 ENST00000566069.6	TSL:5	c.3202-4245T>G	intron	Intron 11 of 11	Prot: ENSP00000459237.2 UniProt:
	PALB2 ENST00000697376.1		c.2317-4245T>G	intron	Intron 12 of 12	Prot: ENSP00000513285.1 UniProt:
	PALB2 ENST00000565038.2	TSL:3	n.*781T>G	3_prime_UTR	Exon 10 of 11	Prot: ENSP00000459882.2 UniProt:
	PALB2 ENST00000697382.1		n.*77T>G	3_prime_UTR	Exon 12 of 13	Prot: ENSP00000513288.1 UniProt:
	PALB2 ENST00000713772.1		n.*689T>G	3_prime_UTR	Exon 12 of 13	Prot: ENSP00000519074.1 UniProt:
	PALB2 ENST00000713773.1		n.*77T>G	3_prime_UTR	Exon 12 of 13	Prot: ENSP00000519075.1 UniProt:
	PALB2 ENST00000565038.2	TSL:3	n.*781T>G	non_coding_transcript_exon	Exon 10 of 11	Prot: ENSP00000459882.2 UniProt:
	PALB2 ENST00000697375.1		n.4647T>G	non_coding_transcript_exon	Exon 11 of 12	Prot:
	PALB2 ENST00000697378.1		n.3820T>G	non_coding_transcript_exon	Exon 12 of 13	Prot:
	PALB2 ENST00000697380.1		n.2504T>G	non_coding_transcript_exon	Exon 6 of 7	Prot:
	PALB2 ENST00000697381.1		n.1995T>G	non_coding_transcript_exon	Exon 9 of 10	Prot:
	PALB2 ENST00000697382.1		n.*77T>G	non_coding_transcript_exon	Exon 12 of 13	Prot: ENSP00000513288.1 UniProt:
	PALB2 ENST00000713772.1		n.*689T>G	non_coding_transcript_exon	Exon 12 of 13	Prot: ENSP00000519074.1 UniProt:
	PALB2 ENST00000713773.1		n.*77T>G	non_coding_transcript_exon	Exon 12 of 13	Prot: ENSP00000519075.1 UniProt:
	PALB2-AS1 ENST00000561764.1	TSL:2	n.185+531A>C	intron	Intron 2 of 3	Prot:

PALB2 ENST00000261584.9

TSL:1MANE Select

HGVSc / HGVSpc.3300T>Gp.Thr1100Thr

Exon rankExon 12 of 13

synonymous

Prot: ENSP00000261584.4UniProt: Q86YC2

PALB2 ENST00000568219.5

TSL:1

HGVSc / HGVSpc.2415T>Gp.Thr805Thr

Exon rankExon 12 of 13

synonymous

Prot: ENSP00000454703.2UniProt: H3BN63

PALB2 ENST00000561514.3

TSL:5

HGVSc / HGVSpc.3306T>Gp.Thr1102Thr

Exon rankExon 12 of 13

synonymous

Prot: ENSP00000460666.3UniProt: A0AA52I2C1

PALB2 ENST00000697379.2

HGVSc / HGVSpc.3306T>Gp.Thr1102Thr

Exon rankExon 13 of 14

synonymous

Prot: ENSP00000513287.2UniProt: A0AA52I2C1

PALB2 ENST00000970391.1

HGVSc / HGVSpc.3228T>Gp.Thr1076Thr

Exon rankExon 11 of 12

synonymous

Prot: ENSP00000640450.1UniProt: A0ACI8VKF7

PALB2 ENST00000697377.2

HGVSc / HGVSpc.3144T>Gp.Thr1048Thr

Exon rankExon 12 of 13

synonymous

Prot: ENSP00000513286.2UniProt: A0A8V8TKZ4

PALB2 ENST00000916249.1

HGVSc / HGVSpc.3138T>Gp.Thr1046Thr

Exon rankExon 11 of 12

synonymous

Prot: ENSP00000586308.1UniProt: A0ACI8ST35

PALB2 ENST00000916250.1

HGVSc / HGVSpc.3021T>Gp.Thr1007Thr

Exon rankExon 10 of 11

synonymous

Prot: ENSP00000586309.1UniProt: A0ACI8SSX0

PALB2 ENST00000697374.1

HGVSc / HGVSpc.2415T>Gp.Thr805Thr

Exon rankExon 12 of 13

synonymous

Prot: ENSP00000513284.1UniProt: H3BN63

PALB2 ENST00000697383.1

HGVSc / HGVSpc.834T>Gp.Thr278Thr

Exon rankExon 8 of 9

synonymous

Prot: ENSP00000513289.1UniProt: A0A8V8TLC8

PALB2 ENST00000853528.1

HGVSc / HGVSpc.147T>Gp.Thr49Thr

Exon rankExon 2 of 3

synonymous

Prot: ENSP00000523587.1UniProt: A0ACI8QTZ5

PALB2 ENST00000713774.1

HGVSc / HGVSpc.3114-4245T>G

Exon rankIntron 10 of 10

intron

Prot: ENSP00000519076.1UniProt: A0AAQ5BGU0

PALB2 ENST00000566069.6

TSL:5

HGVSc / HGVSpc.3202-4245T>G

Exon rankIntron 11 of 11

intron

Prot: ENSP00000459237.2UniProt: I3L1Z5

PALB2 ENST00000697376.1

HGVSc / HGVSpc.2317-4245T>G

Exon rankIntron 12 of 12

intron

Prot: ENSP00000513285.1UniProt: A0A8V8TMK8

PALB2 ENST00000565038.2

TSL:3

HGVSc / HGVSpn.*781T>G

Exon rankExon 10 of 11

3_prime_UTR

Prot: ENSP00000459882.2UniProt: I3L2S5

PALB2 ENST00000697382.1

HGVSc / HGVSpn.*77T>G

Exon rankExon 12 of 13

3_prime_UTR

Prot: ENSP00000513288.1UniProt: A0A8V8TMC9

PALB2 ENST00000713772.1

HGVSc / HGVSpn.*689T>G

Exon rankExon 12 of 13

3_prime_UTR

Prot: ENSP00000519074.1UniProt: A0AAQ5BGY0

PALB2 ENST00000713773.1

HGVSc / HGVSpn.*77T>G

Exon rankExon 12 of 13

3_prime_UTR

Prot: ENSP00000519075.1UniProt: A0AAQ5BGW2

PALB2 ENST00000565038.2

TSL:3

HGVSc / HGVSpn.*781T>G

Exon rankExon 10 of 11

non_coding_transcript_exon

Prot: ENSP00000459882.2UniProt: I3L2S5

PALB2 ENST00000697375.1

HGVSc / HGVSpn.4647T>G

Exon rankExon 11 of 12

non_coding_transcript_exon

Prot:

PALB2 ENST00000697378.1

HGVSc / HGVSpn.3820T>G

Exon rankExon 12 of 13

non_coding_transcript_exon

Prot:

PALB2 ENST00000697380.1

HGVSc / HGVSpn.2504T>G

Exon rankExon 6 of 7

non_coding_transcript_exon

Prot:

PALB2 ENST00000697381.1

HGVSc / HGVSpn.1995T>G

Exon rankExon 9 of 10

non_coding_transcript_exon

Prot:

PALB2 ENST00000697382.1

HGVSc / HGVSpn.*77T>G

Exon rankExon 12 of 13

non_coding_transcript_exon

Prot: ENSP00000513288.1UniProt: A0A8V8TMC9

PALB2 ENST00000713772.1

HGVSc / HGVSpn.*689T>G

Exon rankExon 12 of 13

non_coding_transcript_exon

Prot: ENSP00000519074.1UniProt: A0AAQ5BGY0

PALB2 ENST00000713773.1

HGVSc / HGVSpn.*77T>G

Exon rankExon 12 of 13

non_coding_transcript_exon

Prot: ENSP00000519075.1UniProt: A0AAQ5BGW2

PALB2-AS1 ENST00000561764.1

TSL:2

HGVSc / HGVSpn.185+531A>C

Exon rankIntron 2 of 3

intron

Prot:

Frequencies

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

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0254	AC:3870	Hom:72	AN:152138	Cov:31
GnomAD2 exomes	AF: 0.0237	AC:5950	Hom:	AN:251488	Cov:
GnomAD4 exome	AF: 0.0279	AC:40855	Hom:660	AN:1461824	Cov:32
GnomAD4 genome	AF: 0.0254	AC:3865	Hom:72	AN:152256	Cov:31
TOPMed (Bravo)	AF: 0.0260	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0264	AC:3119	Hom:47	AN:118076	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.0329	AC:77	Hom:2	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.000295	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0233	AC:7	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.0280	AC:364	Hom:	AN:12994	Cov:
GenomeAsia100K	AF: 0.00779	AC:28	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.000138	AC:1	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.0891	AC:179	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0000330	AC:4	Hom:0	AN:122716	Cov:
Turkish Variome	AF: 0.0541	AC:359	Hom:16	AN:6640	Cov:
UK10K	AF: 0.0296	AC:224	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.000335	AC:3	Hom:0	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.0225 *	250	11112	0.0196 *	345	17618
BipEx(Bipolar disorder (including schizoaffective))	0.0255	724	28420	0.0262	757	28844
Epi25(Epilepsy)	0.0284	1191	41958	0.0275	1841	66888
SCHEMA(Schizophrenia)	0.0241	2966	123312	0.0254	4909	193384

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	not provided (5)
-	-	4	Hereditary cancer-predisposing syndrome (4)
-	-	3	Familial cancer of breast (3)
-	-	2	Breast-ovarian cancer, familial, susceptibility to, 5 (2)
-	-	1	Familial cancer of breast;C1835817:Fanconi anemia complementation group N;C3150547:Pancreatic cancer, susceptibility to, 3 (1)
-	-	1	Fanconi anemia complementation group N (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	Malignant tumor of breast (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	14
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.64
GPN-Star LLR	N/A	-1.8
GPN-Star score	N/A	1.8
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	0.30

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

1 normal (RUO)

1 no calibration

2 assays found for this variant.

Research-use-only (RUO) calibration: 0 functionally abnormal (PS3), 1 functionally normal (BS3).

No calibration: 1 assay (score only).

None of these data are clinically calibrated — they are not validated, so interpret them with great caution.

Nucleotide level

Saturation Genome Editing of PALB2 scores

Saturation Genome Editing of PALB2

• Gene: PALB2
• Assay type: Cell proliferation assay
• Mechanism: Loss of function
• Model system: Immortalized human cells
• Score: 0.00428

Classified as

No clinical calibration. Only research-use-only (RUO) calibrations exist for this assay — they are not reliable evidence; treat them with extreme caution.

BS3 strongFunctionally normalRUO ExCALIBR calibration: BS3 Strong (-6)

Nucleotide level

Saturation Genome Editing of PALB2 scores

Saturation Genome Editing of PALB2

• Gene: PALB2
• Assay type: Cell proliferation assay
• Mechanism: Loss of function
• Model system: Immortalized human cells
• Score: 0.00428

Classified as

normalFunctionally Normal

This score is at approximately the 63th percentile of all variants tested in this assay.

This score has not been calibrated against ACMG evidence — shown for context only, not as clinical evidence.

Other links and lift over

dbSNP: rs45516100;

hg19: chr16-23619235;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar