8-33593730-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_024025.3(DUSP26):​c.239G>A​(p.Arg80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: DUSP26 NM_024025.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.99

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19706476).
• BP6: Variant 8-33593730-C-T is Benign according to our data. Variant chr8-33593730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3842922.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP26	NM_024025.3	c.239G>A	p.Arg80His	missense_variant	Exon 3 of 4	ENST00000256261.9	NP_076930.1
DUSP26	NM_001305115.2	c.239G>A	p.Arg80His	missense_variant	Exon 3 of 4		NP_001292044.1
DUSP26	NM_001305116.2	c.239G>A	p.Arg80His	missense_variant	Exon 2 of 3		NP_001292045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP26	ENST00000256261.9	c.239G>A	p.Arg80His	missense_variant	Exon 3 of 4	1	NM_024025.3	ENSP00000256261.4
DUSP26	ENST00000523956.1	c.239G>A	p.Arg80His	missense_variant	Exon 3 of 4	5		ENSP00000429176.1
DUSP26	ENST00000522982.1	c.239G>A	p.Arg80His	missense_variant	Exon 2 of 2	2		ENSP00000430922.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000600 AC: 15 AN: 249878 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135216

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000494 AC: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 27, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.034	D;D;D
Sift4G	Uncertain	0.031	D;D;.
Polyphen		0.072	B;B;.
Vest4		0.16
MutPred		0.58		Loss of MoRF binding (P = 0.0369);Loss of MoRF binding (P = 0.0369);Loss of MoRF binding (P = 0.0369);
MVP		0.79
MPC		0.61
ClinPred		0.16	T
GERP RS		2.8
Varity_R		0.41
gMVP		0.63

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

Other links and lift over

dbSNP: rs779341922; hg19: chr8-33451248;