NM_024675.4:c.-194C>G

Variant names:

• chr16-23641351-G-C
• rs515726054
• NM_024675.4:c.-194C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_024675.4(PALB2):​c.-194C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 997,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: PALB2 NM_024675.4 upstream_gene
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.680
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-23641351-G-C is Benign according to our data. Variant chr16-23641351-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 126572.Status of the report is no_assertion_criteria_provided, 0 stars.

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.-194C>G		upstream_gene	N/A	NP_078951.2
	DCTN5	NM_032486.4	MANE Select	c.-192G>C		upstream_gene	N/A	NP_115875.1	Q9BTE1-1
	PALB2	NM_001407296.1		c.-194C>G		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.-194C>G		upstream_gene	N/A	ENSP00000261584.4	Q86YC2
	DCTN5	ENST00000300087.7	TSL:1 MANE Select	c.-192G>C		upstream_gene	N/A	ENSP00000300087.2	Q9BTE1-1
	PALB2	ENST00000568219.5	TSL:1	c.-1062C>G		upstream_gene	N/A	ENSP00000454703.2	H3BN63

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000592 AC: 5 AN: 844900 Hom.: 0 Cov.: 11 AF XY: 0.00000465 AC XY: 2 AN XY: 429680

African (AFR) AF: 0.000148 AC: 3 AN: 20336

American (AMR) AF: 0.0000749 AC: 2 AN: 26688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18144

East Asian (EAS) AF: 0.00 AC: 0 AN: 33014

South Asian (SAS) AF: 0.00 AC: 0 AN: 59596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 605590

Other (OTH) AF: 0.00 AC: 0 AN: 39060

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74380

African (AFR) AF: 0.000338 AC: 14 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.68
PromoterAI		-0.091	Neutral

Splicing

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

Other links and lift over

dbSNP: rs515726054; hg19: chr16-23652672;