Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_024675.4(PALB2):c.212-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 1,545,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

PALB2
NM_024675.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:9

Conservation

PhyloP100: 0.274

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 16-23636343-GA-G is Benign according to our data. Variant chr16-23636343-GA-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 215535.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024675.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PALB2	NM_024675.4	MANE Select	c.212-10delT	intron	N/A	NP_078951.2
PALB2	NM_001407296.1		c.152-10delT	intron	N/A	NP_001394225.1
PALB2	NM_001407297.1		c.212-10delT	intron	N/A	NP_001394226.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PALB2	ENST00000261584.9	TSL:1 MANE Select	c.212-10delT	intron	N/A	ENSP00000261584.4
PALB2	ENST00000568219.5	TSL:1	c.-674-10delT	intron	N/A	ENSP00000454703.2
PALB2	ENST00000561514.3	TSL:5	c.218-10delT	intron	N/A	ENSP00000460666.3

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

150446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000572

AC:

AN:

192402

AF XY:

0.0000863

show subpopulations

Gnomad AFR exome

AF:

0.000236

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000600

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000753

AC:

105

AN:

1395248

Hom.:

Cov.:

AF XY:

0.0000793

AC XY:

AN XY:

693170

show subpopulations

African (AFR)

AF:

0.000323

AC:

AN:

30920

American (AMR)

AF:

0.0000524

AC:

AN:

38142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25002

East Asian (EAS)

AF:

0.00

AC:

AN:

37430

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5296

European-Non Finnish (NFE)

AF:

0.0000783

AC:

AN:

1072138

Other (OTH)

AF:

0.000122

AC:

AN:

57508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000126

AC:

AN:

150446

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73390

show subpopulations

African (AFR)

AF:

0.000415

AC:

AN:

40950

American (AMR)

AF:

0.0000660

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67498

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Hereditary cancer-predisposing syndrome (3)

Familial cancer of breast (2)

not specified (1)

PALB2-related cancer predisposition (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs766487430

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over