Genetic Variant DUSP22:p.Val143Ile (chr6-348266-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001286555.3(DUSP22):c.427G>A(p.Val143Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00136 in 1,613,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. V143V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 61)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

DUSP22
NM_001286555.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.74

Publications

8 publications found

Variant links:

Genes affected

DUSP22 (HGNC:16077): (dual specificity phosphatase 22) Enables non-membrane spanning protein tyrosine phosphatase activity and protein tyrosine kinase binding activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; negative regulation of focal adhesion assembly; and negative regulation of non-membrane spanning protein tyrosine kinase activity. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in plasma membrane. Part of cytoplasm; filamentous actin; and leading edge of lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

DUSP22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038633347).

BP6

Variant 6-348266-G-A is Benign according to our data. Variant chr6-348266-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3049760.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286555.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP22	NM_001286555.3	MANE Select	c.427G>A	p.Val143Ile	missense	Exon 6 of 7	NP_001273484.1	Q9NRW4-2
DUSP22	NM_020185.6		c.427G>A	p.Val143Ile	missense	Exon 6 of 8	NP_064570.1	Q9NRW4-1
DUSP22	NR_104473.3		n.430G>A		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.427G>A	p.Val143Ile	missense	Exon 6 of 7	ENSP00000397459.2	Q9NRW4-2
DUSP22	ENST00000344450.9	TSL:1	c.427G>A	p.Val143Ile	missense	Exon 6 of 8	ENSP00000345281.5	Q9NRW4-1
DUSP22	ENST00000603453.5	TSL:4	c.118G>A	p.Val40Ile	missense	Exon 5 of 6	ENSP00000474646.1	S4R3M1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00125

AC:

314

AN:

251282

AF XY:

0.00117

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00426

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00138

AC:

2019

AN:

1460940

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

960

AN XY:

726770

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000329

AC:

AN:

33480

American (AMR)

AF:

0.000805

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000255

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00469

AC:

250

AN:

53260

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00146

AC:

1626

AN:

1111282

Other (OTH)

AF:

0.00104

AC:

AN:

60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.289

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00119

AC:

182

AN:

152362

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

74514

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000168

AC:

AN:

41610

American (AMR)

AF:

0.000980

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00166

AC:

113

AN:

68010

Other (OTH)

AF:

0.00189

AC:

AN:

2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.302

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00137

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00141

AC:

171

EpiCase

AF:

0.00158

EpiControl

AF:

0.00154

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DUSP22-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0064

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

4.7

PrimateAI

Benign

0.38

PROVEAN

Benign

0.20

REVEL

Benign

0.18

Sift

Benign

0.071

Sift4G

Benign

0.18

Polyphen

0.073

Vest4

0.48

MVP

0.34

MPC

0.056

ClinPred

0.024

GERP RS

5.8

Varity_R

0.24

gMVP

0.16

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over