16-23641315-C-T

Variant names:

• chr16-23641315-C-T
• rs138200248
• ENST00000697383.1:c.-158G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000697383.1(PALB2):​c.-158G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALB2 ENST00000697383.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000697383.1. 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.-158G>A		upstream_gene	N/A	NP_078951.2
	DCTN5	NM_032486.4	MANE Select	c.-228C>T		upstream_gene	N/A	NP_115875.1	Q9BTE1-1
	PALB2	NM_001407296.1		c.-158G>A		upstream_gene	N/A	NP_001394225.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	ENST00000697383.1		c.-158G>A		5_prime_UTR	Exon 1 of 9	ENSP00000513289.1	A0A8V8TLC8
	PALB2	ENST00000261584.9	TSL:1 MANE Select	c.-158G>A		upstream_gene	N/A	ENSP00000261584.4	Q86YC2
	DCTN5	ENST00000300087.7	TSL:1 MANE Select	c.-228C>T		upstream_gene	N/A	ENSP00000300087.2	Q9BTE1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 941606 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 475992

African (AFR) AF: 0.00 AC: 0 AN: 22380

American (AMR) AF: 0.00 AC: 0 AN: 28774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19584

East Asian (EAS) AF: 0.00 AC: 0 AN: 33494

South Asian (SAS) AF: 0.00 AC: 0 AN: 64840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 686310

Other (OTH) AF: 0.00 AC: 0 AN: 42152

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.44
PromoterAI		0.084	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138200248; hg19: chr16-23652636;