rs1060502752

Variant summary

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

The NM_024675.4(PALB2):​c.3484G>C​(p.Val1162Leu) variant causes a missense change. 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. V1162M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PALB2
NM_024675.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
PALB2NM_024675.4 linkuse as main transcriptc.3484G>C p.Val1162Leu missense_variant 13/13 ENST00000261584.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PALB2ENST00000261584.9 linkuse as main transcriptc.3484G>C p.Val1162Leu missense_variant 13/131 NM_024675.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
2.0
.;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.13
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.022
D;D
Polyphen
1.0
.;D
Vest4
0.60
MutPred
0.23
.;Loss of methylation at K1163 (P = 0.0412);
MVP
0.51
MPC
0.34
ClinPred
0.89
D
GERP RS
5.9
Varity_R
0.51
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr16-23614857; API