rs114491776

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_024675.4(PALB2):c.2834+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,531,466 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: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

PALB2
NM_024675.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0110

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: Ambry Genetics
PALB2-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Fanconi anemia complementation group N
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
pancreatic cancer, susceptibility to, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PALB2 links:

PALB2-AS1 (HGNC:58305):

PALB2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-23623991-T-A is Benign according to our data. Variant chr16-23623991-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00105 (160/152244) while in subpopulation AFR AF = 0.00373 (155/41538). AF 95% confidence interval is 0.00325. There are 0 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.2834+18A>T	intron	N/A	NP_078951.2
PALB2	NM_001407296.1		c.2774+18A>T	intron	N/A	NP_001394225.1
PALB2	NM_001407297.1		c.2762+18A>T	intron	N/A	NP_001394226.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PALB2	ENST00000261584.9	TSL:1 MANE Select	c.2834+18A>T	intron	N/A	ENSP00000261584.4	Q86YC2
PALB2	ENST00000568219.5	TSL:1	c.1949+18A>T	intron	N/A	ENSP00000454703.2	H3BN63
PALB2	ENST00000561514.3	TSL:5	c.2840+18A>T	intron	N/A	ENSP00000460666.3	A0AA52I2C1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000269

AC:

AN:

249084

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.00361

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000914

AC:

126

AN:

1379222

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

690540

show subpopulations

African (AFR)

AF:

0.00329

AC:

104

AN:

31570

American (AMR)

AF:

0.000269

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25676

East Asian (EAS)

AF:

0.00

AC:

AN:

39184

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

9.64e-7

AC:

AN:

1037220

Other (OTH)

AF:

0.000139

AC:

AN:

57604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00105

AC:

160

AN:

152244

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00373

AC:

155

AN:

41538

American (AMR)

AF:

0.000262

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000555

Hom.:

Bravo

AF:

0.00108

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (2)

Hereditary cancer-predisposing syndrome (2)

Breast-ovarian cancer, familial, susceptibility to, 5 (1)

Hereditary breast ovarian cancer syndrome (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.19

(source)

DANN

Benign

0.55

PhyloP100

0.011

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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

Computational scores

Splicing

Publications

Other links and lift over