rs249942

Positions:

• chr16-23634027-C-A
• chr16-23634027-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024675.4(PALB2):​c.1684+835G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,152 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (483 hom., cov: 32)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALB2	NM_024675.4	c.1684+835G>T		intron_variant		ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.1684+835G>T		intron_variant		1	NM_024675.4	ENSP00000261584.4

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11251 AN: 152034 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0740 AC: 11261 AN: 152152 Hom.: 483 Cov.: 32 AF XY: 0.0748 AC XY: 5564 AN XY: 74392

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.0603

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0384 Hom.: 34

Bravo AF: 0.0744

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs249942; hg19: chr16-23645348;