16-23633265-A-G

Variant names:

• chr16-23633265-A-G
• rs16940342
• NM_024675.4:c.1684+1597T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_024675.4(PALB2):​c.1684+1597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,214 control chromosomes in the GnomAD database, including 2,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.18 (2625 hom., cov: 33)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.620
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• Fanconi anemia complementation group N

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• pancreatic cancer, susceptibility to, 3

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• familial ovarian cancer

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-23633265-A-G is Benign according to our data. Variant chr16-23633265-A-G is described in ClinVar as Benign. ClinVar VariationId is 126615.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4	c.1684+1597T>C		intron_variant	Intron 4 of 12	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.1684+1597T>C		intron_variant	Intron 4 of 12	1	NM_024675.4	ENSP00000261584.4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27605 AN: 152094 Hom.: 2616 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.182 AC: 27658 AN: 152214 Hom.: 2625 Cov.: 33 AF XY: 0.185 AC XY: 13760 AN XY: 74434

African (AFR) AF: 0.222 AC: 9226 AN: 41526

American (AMR) AF: 0.192 AC: 2942 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3466

East Asian (EAS) AF: 0.191 AC: 989 AN: 5172

South Asian (SAS) AF: 0.207 AC: 1001 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2261 AN: 10596

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10151 AN: 68022

Other (OTH) AF: 0.175 AC: 371 AN: 2116

Alfa AF: 0.158 Hom.: 2687

Bravo AF: 0.181

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

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.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.54
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16940342; hg19: chr16-23644586;