rs1555459710

Variant names:

• chr16-23624026-C-A
• rs1555459710
• NM_024675.4:c.2817G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-23624026-C-A
• chr16-23624026-C-G
• chr16-23624026-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024675.4(PALB2):​c.2817G>T​(p.Leu939Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L939W) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALB2 NM_024675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	NM_024675.4	MANE Select	c.2817G>T	p.Leu939Phe	missense	Exon 8 of 13	NP_078951.2
	PALB2	NM_001407296.1		c.2757G>T	p.Leu919Phe	missense	Exon 7 of 12	NP_001394225.1
	PALB2	NM_001407297.1		c.2745G>T	p.Leu915Phe	missense	Exon 7 of 12	NP_001394226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	ENST00000261584.9	TSL:1 MANE Select	c.2817G>T	p.Leu939Phe	missense	Exon 8 of 13	ENSP00000261584.4	Q86YC2
	PALB2	ENST00000568219.5	TSL:1	c.1932G>T	p.Leu644Phe	missense	Exon 8 of 13	ENSP00000454703.2	H3BN63
	PALB2	ENST00000561514.3	TSL:5	c.2823G>T	p.Leu941Phe	missense	Exon 8 of 13	ENSP00000460666.3	A0AA52I2C1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.40		Loss of helix (P = 0.1299)
MVP		0.45
MPC		0.36
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.83
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1555459710; hg19: chr16-23635347;