16-23629879-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_024675.4(PALB2):​c.2275C>A​(p.Gln759Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. Q759Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PALB2
NM_024675.4 missense

Scores

19

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.637
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05363694).
BP6
Variant 16-23629879-G-T is Benign according to our data. Variant chr16-23629879-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 126643.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23629879-G-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PALB2NM_024675.4 linkc.2275C>A p.Gln759Lys missense_variant Exon 5 of 13 ENST00000261584.9 NP_078951.2 Q86YC2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PALB2ENST00000261584.9 linkc.2275C>A p.Gln759Lys missense_variant Exon 5 of 13 1 NM_024675.4 ENSP00000261584.4 Q86YC2

Frequencies

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

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Familial cancer of breast Benign:1
May 13, 2019
Leiden Open Variation Database
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: curation

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
8.3
DANN
Benign
0.19
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.095
N
LIST_S2
Benign
0.54
T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.90
.;L
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.032
Sift
Benign
0.55
T;T
Sift4G
Benign
0.75
T;T
Polyphen
0.0080
.;B
Vest4
0.17
MutPred
0.25
.;Gain of solvent accessibility (P = 0.0071);
MVP
0.17
MPC
0.067
ClinPred
0.031
T
GERP RS
-0.54
Varity_R
0.035
gMVP
0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs515726083; hg19: chr16-23641200; API