Variant 16-23629146-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024675.4(PALB2):c.2586+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,332,896 control chromosomes in the GnomAD database, including 48,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7873 hom., cov: 32)

Exomes 𝑓: 0.26 ( 40877 hom. )

Consequence

PALB2
NM_024675.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.329

Variant links:

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]

PALB2 links:

PALB2 (HGNC:):

PALB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-23629146-G-A is Benign according to our data. Variant chr16-23629146-G-A is described in ClinVar as [Benign]. Clinvar id is 126663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629146-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALB2	NM_024675.4 linkuse as main transcript	c.2586+58C>T		intron_variant		ENST00000261584.9	NP_078951.2	Q86YC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9 linkuse as main transcript	c.2586+58C>T		intron_variant		1	NM_024675.4	ENSP00000261584.4		Q86YC2

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47107

AN:

151840

Hom.:

7832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.259

AC:

305341

AN:

1180936

Hom.:

40877

AF XY:

0.260

AC XY:

156052

AN XY:

601128

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.276

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.311

AC:

47213

AN:

151960

Hom.:

7873

Cov.:

AF XY:

0.314

AC XY:

23300

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.253

Hom.:

6566

Bravo

AF:

0.315

Asia WGS

AF:

0.352

AC:

1225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Breast-ovarian cancer, familial, susceptibility to, 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Familial cancer of breast

Benign:1

Benign, no assertion criteria provided

curation

Leiden Open Variation Database

May 13, 2019

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz. -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over