16-23603521-TAC-T

Variant names:

• chr16-23603521-TAC-T
• rs587776427
• NM_024675.4:c.3497_3498delGT

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_024675.4(PALB2):​c.3497_3498delGT​(p.Gly1166AspfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G1166G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALB2 NM_024675.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.0140
• Publications: 0 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_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 17 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-23603521-TAC-T is Pathogenic according to our data. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23603521-TAC-T is described in CliVar as Pathogenic. Clinvar id is 143975.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4	c.3497_3498delGT	p.Gly1166AspfsTer23	frameshift_variant	Exon 13 of 13	ENST00000261584.9	NP_078951.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.3497_3498delGT	p.Gly1166AspfsTer23	frameshift_variant	Exon 13 of 13	1	NM_024675.4	ENSP00000261584.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:1

-

SNPedia

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Familial cancer of breast Pathogenic:1

May 13, 2019

Leiden Open Variation Database

Significance: Pathogenic

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
PhyloP100		-0.014
Mutation Taster		=19/181	disease causing (ClinVar)

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: rs587776427; hg19: chr16-23614842;