rs150730533

chr16-23621231-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_024675.4(PALB2):c.3113+131G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 727,084 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (6 hom.)
• Consequence: PALB2 NM_024675.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.19

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-23621231-C-A is Benign according to our data. Variant chr16-23621231-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 126710.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-23621231-C-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALB2	NM_024675.4	c.3113+131G>T		intron_variant		ENST00000261584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALB2	ENST00000261584.9	c.3113+131G>T		intron_variant		1	NM_024675.4	P1
	ENST00000561764.1	n.420-2669C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00356 AC: 542 AN: 152048 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00978

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00471

Gnomad OTH AF: 0.00864

GnomAD4 exome AF: 0.00356 AC: 2047 AN: 574920 Hom.: 6 AF XY: 0.00334 AC XY: 1031 AN XY: 308806

Gnomad4 AFR exome AF: 0.000634

Gnomad4 AMR exome AF: 0.00551

Gnomad4 ASJ exome AF: 0.00487

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000535

Gnomad4 FIN exome AF: 0.000512

Gnomad4 NFE exome AF: 0.00462

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00356 AC: 542 AN: 152164 Hom.: 2 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74428

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00976

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00471

Gnomad4 OTH AF: 0.00855

Alfa AF: 0.00391 Hom.: 0

Bravo AF: 0.00448

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.70
Dann	Benign	0.48

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: rs150730533; hg19: chr16-23632552;