rs8053188

Variant names:

• chr16-23641204-C-T
• rs8053188
• NM_024675.4:c.-47G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024675.4(PALB2):​c.-47G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,599,550 control chromosomes in the GnomAD database, including 1,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (308 hom., cov: 32)
  • Exomes 𝑓: 0.026 (857 hom.)
• Consequence: PALB2 NM_024675.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.02
• Publications: 18 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]

DCTN5 (HGNC:24594): (dynactin subunit 5) This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-23641204-C-T is Benign according to our data. Variant chr16-23641204-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 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.-47G>A		5_prime_UTR	Exon 1 of 13	NP_078951.2
	PALB2	NM_001407296.1		c.-47G>A		5_prime_UTR	Exon 1 of 12	NP_001394225.1
	PALB2	NM_001407297.1		c.-47G>A		5_prime_UTR	Exon 1 of 12	NP_001394226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	ENST00000261584.9	TSL:1 MANE Select	c.-47G>A		5_prime_UTR	Exon 1 of 13	ENSP00000261584.4	Q86YC2
	PALB2	ENST00000568219.5	TSL:1	c.-915G>A		5_prime_UTR	Exon 1 of 13	ENSP00000454703.2	H3BN63
	PALB2	ENST00000561514.3	TSL:5	c.-899G>A		5_prime_UTR	Exon 1 of 13	ENSP00000460666.3	A0AA52I2C1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7528 AN: 152210 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0488

GnomAD2 exomes AF: 0.0401 AC: 8852 AN: 220560 AF XY: 0.0381

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0821

Gnomad ASJ exome AF: 0.0545

Gnomad EAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0368

GnomAD4 exome AF: 0.0262 AC: 37889 AN: 1447222 Hom.: 857 Cov.: 30 AF XY: 0.0267 AC XY: 19204 AN XY: 718822

African (AFR) AF: 0.0972 AC: 3227 AN: 33214

American (AMR) AF: 0.0850 AC: 3635 AN: 42788

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 1371 AN: 25738

East Asian (EAS) AF: 0.00846 AC: 332 AN: 39226

South Asian (SAS) AF: 0.0529 AC: 4460 AN: 84310

European-Finnish (FIN) AF: 0.0238 AC: 1244 AN: 52210

Middle Eastern (MID) AF: 0.0460 AC: 205 AN: 4460

European-Non Finnish (NFE) AF: 0.0193 AC: 21389 AN: 1105608

Other (OTH) AF: 0.0340 AC: 2026 AN: 59668

GnomAD4 genome AF: 0.0497 AC: 7574 AN: 152328 Hom.: 308 Cov.: 32 AF XY: 0.0506 AC XY: 3769 AN XY: 74506

African (AFR) AF: 0.0981 AC: 4078 AN: 41578

American (AMR) AF: 0.0801 AC: 1225 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3470

East Asian (EAS) AF: 0.00869 AC: 45 AN: 5178

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4826

European-Finnish (FIN) AF: 0.0228 AC: 242 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1449 AN: 68028

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0402 Hom.: 53

Bravo AF: 0.0532

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	not provided (2)
-	-	1	Familial cancer of breast (1)
-	-	1	Fanconi anemia complementation group N (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		1.0
PromoterAI		-0.13	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8053188; hg19: chr16-23652525; COSMIC: COSV55166576; COSMIC: COSV55166576;