rs878855107

chr16-23629953-G-Achr16-23629953-G-Cchr16-23629953-G-T

Variant summary

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

The NM_024675.4(PALB2):c.2201C>T(p.Thr734Ile) 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. T734N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALB2 NM_024675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58

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]

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.2201C>T	p.Thr734Ile	missense_variant	5/13	ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.2201C>T	p.Thr734Ile	missense_variant	5/13	1	NM_024675.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.34	T;D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D;D
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	.;D
Vest4		0.70
MutPred		0.38		.;Loss of glycosylation at T734 (P = 0.0144);
MVP		0.80
MPC		0.36
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.61
gMVP		0.59

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: chr16-23641274;