dbSNP rs8053188: PALB2:c.-47G>A (chr16-23641204-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_024675.4(PALB2):c.-47G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,599,550 control chromosomes in the GnomAD database, including 1,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 308 hom., cov: 32)

Exomes 𝑓: 0.026 ( 857 hom. )

Consequence

PALB2
NM_024675.4 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.02

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:

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=-0.64).

BP6

Variant 16-23641204-C-T is Benign according to our data. Variant chr16-23641204-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 126578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23641204-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4 link	c.-47G>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000261584.9	NP_078951.2	Q86YC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9 link	c.-47G>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_024675.4	ENSP00000261584.4		Q86YC2

Frequencies

GnomAD3 genomes

AF:

0.0495

AC:

7528

AN:

152210

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0797

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.00867

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0401

AC:

8852

AN:

220560

Hom.:

288

AF XY:

0.0381

AC XY:

4601

AN XY:

120606

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0821

Gnomad ASJ exome

AF:

0.0545

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.0563

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0368

GnomAD4 exome

AF:

0.0262

AC:

37889

AN:

1447222

Hom.:

857

Cov.:

AF XY:

0.0267

AC XY:

19204

AN XY:

718822

show subpopulations

Gnomad4 AFR exome

AF:

0.0972

Gnomad4 AMR exome

AF:

0.0850

Gnomad4 ASJ exome

AF:

0.0533

Gnomad4 EAS exome

AF:

0.00846

Gnomad4 SAS exome

AF:

0.0529

Gnomad4 FIN exome

AF:

0.0238

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0340

GnomAD4 genome

AF:

0.0497

AC:

7574

AN:

152328

Hom.:

308

Cov.:

AF XY:

0.0506

AC XY:

3769

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0981

Gnomad4 AMR

AF:

0.0801

Gnomad4 ASJ

AF:

0.0481

Gnomad4 EAS

AF:

0.00869

Gnomad4 SAS

AF:

0.0539

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0213

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0365

Hom.:

Bravo

AF:

0.0532

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia complementation group N

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary cancer-predisposing syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast

Benign:1

May 13, 2019

Leiden Open Variation Database

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

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

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.89

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

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