rs447529

Variant names:

• chr16-23622102-C-G
• rs447529
• NM_024675.4:c.2997-624G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_024675.4(PALB2):​c.2997-624G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,100 control chromosomes in the GnomAD database, including 1,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.13 (1517 hom., cov: 32)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.246
• Publications: 8 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: 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-AS1 (HGNC:58305):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 16-23622102-C-G is Benign according to our data. Variant chr16-23622102-C-G is described in ClinVar as Benign. ClinVar VariationId is 126704.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	NM_024675.4	MANE Select	c.2997-624G>C		intron	N/A	NP_078951.2
	PALB2	NM_001407296.1		c.2937-624G>C		intron	N/A	NP_001394225.1
	PALB2	NM_001407297.1		c.2925-624G>C		intron	N/A	NP_001394226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	ENST00000261584.9	TSL:1 MANE Select	c.2997-624G>C		intron	N/A	ENSP00000261584.4	Q86YC2
	PALB2	ENST00000568219.5	TSL:1	c.2112-624G>C		intron	N/A	ENSP00000454703.2	H3BN63
	PALB2	ENST00000561514.3	TSL:5	c.3003-624G>C		intron	N/A	ENSP00000460666.3	A0AA52I2C1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19518 AN: 151982 Hom.: 1506 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.0907

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.129 AC: 19566 AN: 152100 Hom.: 1517 Cov.: 32 AF XY: 0.128 AC XY: 9553 AN XY: 74352

African (AFR) AF: 0.214 AC: 8879 AN: 41474

American (AMR) AF: 0.0982 AC: 1499 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 315 AN: 3472

East Asian (EAS) AF: 0.173 AC: 897 AN: 5182

South Asian (SAS) AF: 0.104 AC: 499 AN: 4810

European-Finnish (FIN) AF: 0.0932 AC: 985 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6014 AN: 68002

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.113 Hom.: 152

Bravo AF: 0.134

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.26
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs447529; hg19: chr16-23633423;