chr16-23629685-G-T

Variant names:

• chr16-23629685-G-T
• rs515726087
• NM_024675.4:c.2469C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024675.4(PALB2):​c.2469C>A​(p.Leu823Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L823L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALB2 NM_024675.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.24
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-23629685-G-T is Benign according to our data. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23629685-G-T is described in CliVar as Benign. Clinvar id is 126654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4	c.2469C>A	p.Leu823Leu	synonymous_variant	Exon 5 of 13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.2469C>A	p.Leu823Leu	synonymous_variant	Exon 5 of 13	1	NM_024675.4	ENSP00000261584.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Familial cancer of breast Benign:2

Jan 16, 2025

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

May 13, 2019

Leiden Open Variation Database

Significance: Likely 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	0.63
DANN	Benign	0.73
PhyloP100		-1.2

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: rs515726087; hg19: chr16-23641006;