chr8-33592123-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024025.3(DUSP26):​c.526G>A​(p.Val176Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DUSP26
NM_024025.3 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DUSP26NM_024025.3 linkc.526G>A p.Val176Met missense_variant Exon 4 of 4 ENST00000256261.9 NP_076930.1 Q9BV47-1
DUSP26NM_001305115.2 linkc.526G>A p.Val176Met missense_variant Exon 4 of 4 NP_001292044.1 Q9BV47-1
DUSP26NM_001305116.2 linkc.526G>A p.Val176Met missense_variant Exon 3 of 3 NP_001292045.1 Q9BV47-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DUSP26ENST00000256261.9 linkc.526G>A p.Val176Met missense_variant Exon 4 of 4 1 NM_024025.3 ENSP00000256261.4 Q9BV47-1
DUSP26ENST00000523956.1 linkc.526G>A p.Val176Met missense_variant Exon 4 of 4 5 ENSP00000429176.1 Q9BV47-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152058
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249042
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134802
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461862
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.526G>A (p.V176M) alteration is located in exon 4 (coding exon 3) of the DUSP26 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the valine (V) at amino acid position 176 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Uncertain
0.16
D
MutationAssessor
Benign
1.9
L;L
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.48
Sift
Benign
0.069
T;T
Sift4G
Uncertain
0.013
D;D
Polyphen
0.96
D;D
Vest4
0.49
MutPred
0.46
Loss of catalytic residue at V176 (P = 0.0875);Loss of catalytic residue at V176 (P = 0.0875);
MVP
0.91
MPC
1.4
ClinPred
0.75
D
GERP RS
4.8
Varity_R
0.24
gMVP
0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs545078102; hg19: chr8-33449641; COSMIC: COSV56362697; COSMIC: COSV56362697; API