8-33593566-C-T

Variant names:

• chr8-33593566-C-T
• rs147101666
• NM_024025.3:c.403G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024025.3(DUSP26):​c.403G>A​(p.Asp135Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000322 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: DUSP26 NM_024025.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13893622).

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.403G>A	p.Asp135Asn	missense	Exon 3 of 4	NP_076930.1	Q9BV47-1
	DUSP26	NM_001305115.2		c.403G>A	p.Asp135Asn	missense	Exon 3 of 4	NP_001292044.1	Q9BV47-1
	DUSP26	NM_001305116.2		c.403G>A	p.Asp135Asn	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.403G>A	p.Asp135Asn	missense	Exon 3 of 4	ENSP00000256261.4	Q9BV47-1
	DUSP26	ENST00000523956.1	TSL:5	c.403G>A	p.Asp135Asn	missense	Exon 3 of 4	ENSP00000429176.1	Q9BV47-1
	DUSP26	ENST00000854271.1		c.403G>A	p.Asp135Asn	missense	Exon 3 of 4	ENSP00000524330.1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000335 AC: 84 AN: 251110 AF XY: 0.000346

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000298 AC: 435 AN: 1461742 Hom.: 0 Cov.: 33 AF XY: 0.000297 AC XY: 216 AN XY: 727134

African (AFR) AF: 0.00102 AC: 34 AN: 33478

American (AMR) AF: 0.000760 AC: 34 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.000233 AC: 259 AN: 1111894

Other (OTH) AF: 0.000861 AC: 52 AN: 60394

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152280 Hom.: 0 Cov.: 31 AF XY: 0.000645 AC XY: 48 AN XY: 74462

African (AFR) AF: 0.000602 AC: 25 AN: 41562

American (AMR) AF: 0.00164 AC: 25 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68018

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000378 Hom.: 5

Bravo AF: 0.000450

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000354 AC: 43

EpiCase AF: 0.000545

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.32	T
Polyphen		0.58	P
Vest4		0.27
MVP		0.82
MPC		1.4
ClinPred		0.019	T
GERP RS		4.8
Varity_R		0.45
gMVP		0.52
Mutation Taster		=42/58	disease causing

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: rs147101666; hg19: chr8-33451084;