rs515726062

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024675.4(PALB2):​c.1095G>T​(p.Arg365Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PALB2
NM_024675.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.133
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16689369).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PALB2NM_024675.4 linkuse as main transcriptc.1095G>T p.Arg365Ser missense_variant 4/13 ENST00000261584.9 NP_078951.2 Q86YC2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PALB2ENST00000261584.9 linkuse as main transcriptc.1095G>T p.Arg365Ser missense_variant 4/131 NM_024675.4 ENSP00000261584.4 Q86YC2

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
8.4
DANN
Uncertain
0.97
DEOGEN2
Benign
0.16
T;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.14
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.038
D;D
Polyphen
0.98
.;D
Vest4
0.21
MutPred
0.32
.;Gain of relative solvent accessibility (P = 0.0166);
MVP
0.49
MPC
0.12
ClinPred
0.77
D
GERP RS
3.7
Varity_R
0.19
gMVP
0.32

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: chr16-23646772; API