rs515726058

Variant names:

• chr16-23641255-G-A
• rs515726058
• NM_024675.4:c.-98C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-23641255-G-A
• chr16-23641255-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024675.4(PALB2):​c.-98C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 1,317,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: PALB2 NM_024675.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALB2	NM_024675.4	c.-98C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000261584.9	NP_078951.2
DCTN5	NM_032486.4	c.-288G>A		upstream_gene_variant		ENST00000300087.7	NP_115875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALB2	ENST00000261584.9	c.-98C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_024675.4	ENSP00000261584.4
DCTN5	ENST00000300087.7	c.-288G>A		upstream_gene_variant		1	NM_032486.4	ENSP00000300087.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000531 AC: 7 AN: 1317238 Hom.: 0 Cov.: 20 AF XY: 0.00000458 AC XY: 3 AN XY: 654380

African (AFR) AF: 0.00 AC: 0 AN: 30116

American (AMR) AF: 0.00 AC: 0 AN: 35856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24434

East Asian (EAS) AF: 0.00 AC: 0 AN: 36150

South Asian (SAS) AF: 0.00 AC: 0 AN: 78968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.00000697 AC: 7 AN: 1004122

Other (OTH) AF: 0.00 AC: 0 AN: 55038

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.86
PhyloP100		-0.20
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs515726058; hg19: chr16-23652576;