rs180177144

Variant names:

• chr16-23641333-C-A
• rs180177144
• NM_024675.4:c.-176G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-23641333-C-A
• chr16-23641333-C-T

Variant summary

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

The NM_024675.4(PALB2):​c.-176G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000117 in 857,730 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: 0.0000012 (0 hom.)
• Consequence: PALB2 NM_024675.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• 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: 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=-0.46).

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.-176G>T		upstream_gene	N/A	NP_078951.2
	DCTN5	NM_032486.4	MANE Select	c.-210C>A		upstream_gene	N/A	NP_115875.1	Q9BTE1-1
	PALB2	NM_001407296.1		c.-176G>T		upstream_gene	N/A	NP_001394225.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALB2	ENST00000261584.9	TSL:1 MANE Select	c.-176G>T		upstream_gene	N/A	ENSP00000261584.4	Q86YC2
	DCTN5	ENST00000300087.7	TSL:1 MANE Select	c.-210C>A		upstream_gene	N/A	ENSP00000300087.2	Q9BTE1-1
	PALB2	ENST00000568219.5	TSL:1	c.-1044G>T		upstream_gene	N/A	ENSP00000454703.2	H3BN63

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 857730 Hom.: 0 Cov.: 11 AF XY: 0.00000230 AC XY: 1 AN XY: 435550

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20666

American (AMR) AF: 0.00 AC: 0 AN: 27002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18354

East Asian (EAS) AF: 0.00 AC: 0 AN: 33064

South Asian (SAS) AF: 0.00 AC: 0 AN: 60602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00000162 AC: 1 AN: 616276

Other (OTH) AF: 0.00 AC: 0 AN: 39386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.80
PhyloP100		0.44
PromoterAI		-0.33	Neutral

Splicing

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

Other links and lift over

dbSNP: rs180177144; hg19: chr16-23652654;