Variant 2-96145138-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004418.4(DUSP2):c.217G>C(p.Asp73His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,193,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DUSP2
NM_004418.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.896

Variant links:

Genes affected

DUSP2 (HGNC:3068): (dual specificity phosphatase 2) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1 and ERK2, is predominantly expressed in hematopoietic tissues, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

DUSP2 links:

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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/exons	MANE	UniProt
DUSP2	NM_004418.4 linkuse as main transcript	c.217G>C	p.Asp73His	missense_variant	1/4	ENST00000288943.5
DUSP2	XM_017003546.2 linkuse as main transcript	c.217G>C	p.Asp73His	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP2	ENST00000288943.5 linkuse as main transcript	c.217G>C	p.Asp73His	missense_variant	1/4	1	NM_004418.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1193316

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

581850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000121

Gnomad4 OTH exome

AF:

0.0000411

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.217G>C (p.D73H) alteration is located in exon 1 (coding exon 1) of the DUSP2 gene. This alteration results from a G to C substitution at nucleotide position 217, causing the aspartic acid (D) at amino acid position 73 to be replaced by a histidine (H). 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

0.59

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.41

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.25

Sift

Uncertain

0.013

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.22

MutPred

0.54

Gain of sheet (P = 0.0061);

MVP

0.66

MPC

2.5

ClinPred

0.93

GERP RS

4.1

Varity_R

0.33

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over