NM_024675.4:c.1809A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_024675.4(PALB2):c.1809A>G(p.Leu603Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PALB2
NM_024675.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.124

Publications

0 publications found

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 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

PALB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-23630345-T-C is Benign according to our data. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23630345-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 241534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.124 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4 link	c.1809A>G	p.Leu603Leu	synonymous_variant	Exon 5 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.1809A>G	p.Leu603Leu	synonymous_variant	Exon 5 of 13	1	NM_024675.4	ENSP00000261584.4		Q86YC2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial cancer of breast

Benign:2

Jan 14, 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. -

Oct 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Aug 08, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.39

PhyloP100

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over