rs249935

chr16-23613903-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024675.4(PALB2):c.3201+101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 829,980 control chromosomes in the GnomAD database, including 5,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1533 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3959 hom.)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-23613903-T-C is Benign according to our data. Variant chr16-23613903-T-C is described in ClinVar as [Benign]. Clinvar id is 1292399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23613903-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALB2	NM_024675.4	c.3201+101A>G		intron_variant		ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.3201+101A>G		intron_variant		1	NM_024675.4	P1
	ENST00000561764.1	n.186-3697T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19558 AN: 152010 Hom.: 1522 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0883

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0998 AC: 67645 AN: 677852 Hom.: 3959 AF XY: 0.0994 AC XY: 35470 AN XY: 356678

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.0843

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0927

Gnomad4 NFE exome AF: 0.0891

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.129 AC: 19606 AN: 152128 Hom.: 1533 Cov.: 32 AF XY: 0.129 AC XY: 9584 AN XY: 74394

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.0883

Gnomad4 OTH AF: 0.127

Alfa AF: 0.113 Hom.: 152

Bravo AF: 0.135

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Hereditary breast ovarian cancer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.30
Dann	Benign	0.27

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: rs249935; hg19: chr16-23625224; COSMIC: COSV55163493;