rs199767268

chr16-23622785-CT-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_024675.4(PALB2):c.2996+183del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 152,236 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0071 (15 hom., cov: 32)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.528

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-23622785-CT-C is Benign according to our data. Variant chr16-23622785-CT-C is described in ClinVar as [Benign]. Clinvar id is 126702.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-23622785-CT-C is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALB2	NM_024675.4	c.2996+183del		intron_variant		ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.2996+183del		intron_variant		1	NM_024675.4	P1
	ENST00000561764.1	n.420-1114del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00713 AC: 1085 AN: 152118 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00288

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

GnomAD4 genome AF: 0.00713 AC: 1085 AN: 152236 Hom.: 15 Cov.: 32 AF XY: 0.00884 AC XY: 658 AN XY: 74426

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.00689

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00543 Hom.: 0

Bravo AF: 0.00338

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Familial cancer of breast Benign:1

Likely 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

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

LitVar

Other links and lift over

dbSNP: rs199767268; hg19: chr16-23634106;