chr8-33593566-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 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. 13/21 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

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13893622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP26	NM_024025.3	c.403G>A	p.Asp135Asn	missense_variant	Exon 3 of 4	ENST00000256261.9	NP_076930.1
DUSP26	NM_001305115.2	c.403G>A	p.Asp135Asn	missense_variant	Exon 3 of 4		NP_001292044.1
DUSP26	NM_001305116.2	c.403G>A	p.Asp135Asn	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.403G>A	p.Asp135Asn	missense_variant	Exon 3 of 4	1	NM_024025.3	ENSP00000256261.4
DUSP26	ENST00000523956.1	c.403G>A	p.Asp135Asn	missense_variant	Exon 3 of 4	5		ENSP00000429176.1
DUSP26	ENST00000522982.1	c.403G>A	p.Asp135Asn	missense_variant	Exon 2 of 2	2		ENSP00000430922.1

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

GnomAD3 exomes AF: 0.000335 AC: 84 AN: 251110 Hom.: 0 AF XY: 0.000346 AC XY: 47 AN XY: 135776

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 SAS exome AF: 0.000229

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

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000233

Gnomad4 OTH exome AF: 0.000861

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

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000344 Hom.: 0

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.403G>A (p.D135N) alteration is located in exon 3 (coding exon 2) of the DUSP26 gene. This alteration results from a G to A substitution at nucleotide position 403, causing the aspartic acid (D) at amino acid position 135 to be replaced by an asparagine (N). 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	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;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.32	T;T;.
Polyphen		0.58	P;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

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: rs147101666; hg19: chr8-33451084;