chr8-33593730-C-A

Variant names:

• chr8-33593730-C-A
• rs779341922
• NM_024025.3:c.239G>T

Variant summary

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

The NM_024025.3(DUSP26):​c.239G>T​(p.Arg80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R80H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DUSP26 NM_024025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26124567).

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.239G>T	p.Arg80Leu	missense	Exon 3 of 4	NP_076930.1	Q9BV47-1
	DUSP26	NM_001305115.2		c.239G>T	p.Arg80Leu	missense	Exon 3 of 4	NP_001292044.1	Q9BV47-1
	DUSP26	NM_001305116.2		c.239G>T	p.Arg80Leu	missense	Exon 2 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.239G>T	p.Arg80Leu	missense	Exon 3 of 4	ENSP00000256261.4	Q9BV47-1
	DUSP26	ENST00000523956.1	TSL:5	c.239G>T	p.Arg80Leu	missense	Exon 3 of 4	ENSP00000429176.1	Q9BV47-1
	DUSP26	ENST00000854271.1		c.239G>T	p.Arg80Leu	missense	Exon 3 of 4	ENSP00000524330.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249878 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.065	N
PhyloP100		2.0
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.099
Sift	Benign	0.061	T
Sift4G	Benign	0.11	T
Polyphen		0.026	B
Vest4		0.37
MutPred		0.56		Loss of disorder (P = 0.0375)
MVP		0.46
MPC		0.61
ClinPred		0.89	D
GERP RS		2.8
Varity_R		0.64
gMVP		0.75
Mutation Taster		=64/36	polymorphism

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: rs779341922; hg19: chr8-33451248;