chr8-33597460-C-A

Variant names:

• chr8-33597460-C-A
• rs753004086
• NM_024025.3:c.56G>T

Variant summary

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

The NM_024025.3(DUSP26):​c.56G>T​(p.Arg19Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUSP26 NM_024025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69
• Publications: 5 publications found

Genes affected

DUSP26 (HGNC:28161): (dual specificity phosphatase 26) This gene encodes a member of the tyrosine phosphatase family of proteins and exhibits dual specificity by dephosphorylating tyrosine as well as serine and threonine residues. This gene has been described as both a tumor suppressor and an oncogene depending on the cellular context. This protein may regulate neuronal proliferation and has been implicated in the progression of glioblastoma through its ability to dephosphorylate the p53 tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024025.3. 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
	DUSP26	NM_024025.3	MANE Select	c.56G>T	p.Arg19Leu	missense	Exon 2 of 4	NP_076930.1	Q9BV47-1
	DUSP26	NM_001305115.2		c.56G>T	p.Arg19Leu	missense	Exon 2 of 4	NP_001292044.1	Q9BV47-1
	DUSP26	NM_001305116.2		c.56G>T	p.Arg19Leu	missense	Exon 1 of 3	NP_001292045.1	Q9BV47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP26	ENST00000256261.9	TSL:1 MANE Select	c.56G>T	p.Arg19Leu	missense	Exon 2 of 4	ENSP00000256261.4	Q9BV47-1
	DUSP26	ENST00000523956.1	TSL:5	c.56G>T	p.Arg19Leu	missense	Exon 2 of 4	ENSP00000429176.1	Q9BV47-1
	DUSP26	ENST00000854271.1		c.56G>T	p.Arg19Leu	missense	Exon 2 of 4	ENSP00000524330.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.42	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.018	D
Sift4G	Benign	0.28	T
Polyphen		0.99	D
Vest4		0.90
MutPred		0.41		Loss of helix (P = 3e-04)
MVP		0.67
MPC		1.5
ClinPred		0.91	D
GERP RS		5.5
PromoterAI		-0.020	Neutral
Varity_R		0.16
gMVP		0.61
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs753004086; hg19: chr8-33454978;