chr16-23637951-C-G

Position:

• chr16-23637951-C-G

Variant summary

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

The ENST00000261584.9(PALB2):​c.110G>C​(p.Arg37Pro) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R37S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALB2 ENST00000261584.9 missense, splice_region
• Scores: Splicing: ADA: 0.04516
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.37

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	Protein	UniProt
PALB2	NM_024675.4	c.110G>C	p.Arg37Pro	missense_variant, splice_region_variant	3/13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.110G>C	p.Arg37Pro	missense_variant, splice_region_variant	3/13	1	NM_024675.4	ENSP00000261584	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.8	D;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.014	D;.
Polyphen		1.0	D;.
Vest4		0.85
MutPred		0.30		Loss of helix (P = 0.0304);.;
MVP		0.86
MPC		0.40
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.91
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.045
dbscSNV1_RF	Benign	0.35
SpliceAI score (max)		0.010		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: chr16-23649272;