16-23623060-C-G

Position:

• chr16-23623060-C-G

Variant summary

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

The NM_024675.4(PALB2):​c.2905G>C​(p.Val969Leu) 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. V969A) has been classified as Uncertain significance.

• 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	UniProt
PALB2	NM_024675.4	c.2905G>C	p.Val969Leu	missense_variant	9/13	ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.2905G>C	p.Val969Leu	missense_variant	9/13	1	NM_024675.4	P1
	ENST00000561764.1	n.420-840C>G		intron_variant, non_coding_transcript_variant		2

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	0.098
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	0.89	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.091
Sift	Benign	0.085	T;T
Sift4G	Benign	0.078	T;D
Polyphen		0.43	.;B
Vest4		0.63
MutPred		0.37		.;Loss of sheet (P = 0.0084);
MVP		0.41
MPC		0.20
ClinPred		0.84	D
GERP RS		3.8
Varity_R		0.36
gMVP		0.52

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: chr16-23634381;