16-23634820-TTCATCATCA-TTCATCATCATCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_024675.4(PALB2):c.1684+39_1684+41dupTGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,582,734 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). The gene PALB2 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 22 hom. )

Consequence

PALB2
NM_024675.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.231

Publications

1 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:

Genome browser will be placed here

ACMG classification

Specifications for PALB2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

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

BP6

Variant 16-23634820-T-TTCA is Benign according to our data. Variant chr16-23634820-T-TTCA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00209 (318/152040) while in subpopulation SAS AF = 0.00998 (48/4812). AF 95% confidence interval is 0.00773. There are 2 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

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.1684+39_1684+41dupTGA	intron	N/A	NP_078951.2
PALB2	NM_001407296.1		c.1624+39_1624+41dupTGA	intron	N/A	NP_001394225.1
PALB2	NM_001407297.1		c.1684+39_1684+41dupTGA	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.1684+41_1684+42insTGA	intron	N/A	ENSP00000261584.4	Q86YC2
PALB2	ENST00000568219.5	TSL:1	c.799+41_799+42insTGA	intron	N/A	ENSP00000454703.2	H3BN63
PALB2	ENST00000561514.3	TSL:5	c.1690+41_1690+42insTGA	intron	N/A	ENSP00000460666.3	A0AA52I2C1

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

314

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00976

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00393

AC:

778

AN:

198064

AF XY:

0.00452

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.000390

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.00251

AC:

3587

AN:

1430694

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

1963

AN XY:

709646

show subpopulations

African (AFR)

AF:

0.000398

AC:

AN:

32698

American (AMR)

AF:

0.00138

AC:

AN:

39102

Ashkenazi Jewish (ASJ)

AF:

0.0244

AC:

626

AN:

25612

East Asian (EAS)

AF:

0.00345

AC:

133

AN:

38496

South Asian (SAS)

AF:

0.0102

AC:

843

AN:

83022

European-Finnish (FIN)

AF:

0.000621

AC:

AN:

51520

Middle Eastern (MID)

AF:

0.00998

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00144

AC:

1572

AN:

1095136

Other (OTH)

AF:

0.00433

AC:

257

AN:

59398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

180

359

539

718

898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.00209

AC:

318

AN:

152040

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

164

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.000434

AC:

AN:

41494

American (AMR)

AF:

0.00111

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3466

East Asian (EAS)

AF:

0.00193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00998

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00183

AC:

124

AN:

67942

Other (OTH)

AF:

0.00143

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00350

Hom.:

Bravo

AF:

0.00193

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Breast and/or ovarian cancer (1)

Familial cancer of breast (1)

Hereditary breast ovarian cancer syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over