rs447529

Positions:

• chr16-23622102-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 126704.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23622102-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALB2	NM_024675.4	c.2997-624G>C		intron_variant		ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.2997-624G>C		intron_variant		1	NM_024675.4	P1
	ENST00000561764.1	n.420-1798C>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.0907

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.128

Alfa AF: 0.113 Hom.: 152

Bravo AF: 0.134

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Benign:1

Benign, no assertion criteria provided

curation

Leiden Open Variation Database

May 13, 2019

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs447529; hg19: chr16-23633423;