16-23623116-G-T

Position:

• chr16-23623116-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024675.4(PALB2):​c.2849C>A​(p.Ser950Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36034715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALB2	NM_024675.4	c.2849C>A	p.Ser950Tyr	missense_variant	9/13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.2849C>A	p.Ser950Tyr	missense_variant	9/13	1	NM_024675.4	ENSP00000261584.4

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	0.15
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.094	T;T
Eigen	Benign	0.0086
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.94	.;P
Vest4		0.55
MutPred		0.32		.;Loss of disorder (P = 0.0127);
MVP		0.69
MPC		0.32
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.25
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23634437;