rs45624036

Positions:

• chr16-23624049-C-A
• chr16-23624049-C-G
• chr16-23624049-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024675.4(PALB2):​c.2794G>T​(p.Val932Leu) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V932M) 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: 2.32

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALB2	NM_024675.4	c.2794G>T	p.Val932Leu	missense_variant	8/13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.2794G>T	p.Val932Leu	missense_variant	8/13	1	NM_024675.4	ENSP00000261584	P1
	ENST00000561764.1	n.569C>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	0.68	D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.12
Sift	Benign	0.088	T;T
Sift4G	Uncertain	0.034	D;D
Polyphen		1.0	.;D
Vest4		0.66
MutPred		0.24		.;Gain of helix (P = 0.0199);
MVP		0.59
MPC		0.28
ClinPred		0.97	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23635370;