16-23607978-G-C

Position:

• chr16-23607978-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024675.4(PALB2):​c.3236C>G​(p.Ala1079Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1079S) 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: 2.17

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22975534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALB2	NM_024675.4	c.3236C>G	p.Ala1079Gly	missense_variant	12/13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.3236C>G	p.Ala1079Gly	missense_variant	12/13	1	NM_024675.4	ENSP00000261584	P1
	ENST00000561764.1	n.185+595G>C		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	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	0.088
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	0.80	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.086
Sift	Benign	0.14	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.069	.;B
Vest4		0.31
MutPred		0.14		.;Gain of sheet (P = 0.0344);
MVP		0.42
MPC		0.070
ClinPred		0.72	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
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: chr16-23619299;