Genetic Variant DUSP28:p.Pro61Ser (chr2-240560865-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370465.2(DUSP28):c.181C>T(p.Pro61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,363,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

DUSP28
NM_001370465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488

Publications

0 publications found

Variant links:

Genes affected

DUSP28 (HGNC:33237): (dual specificity phosphatase 28) Enables phosphatase activity. Involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

DUSP28 links:

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKMY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04337555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370465.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP28	NM_001370465.2	MANE Select	c.181C>T	p.Pro61Ser	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
ANKMY1	NM_001308375.4		c.86G>A	p.Gly29Asp	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
DUSP28	NM_001033575.1		c.181C>T	p.Pro61Ser	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.181C>T	p.Pro61Ser	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
ANKMY1	ENST00000403283.6	TSL:1	c.86G>A	p.Gly29Asp	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
ANKMY1	ENST00000464991.5	TSL:1	n.581G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

148210

Hom.:

Cov.:

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:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000132

AC:

AN:

53172

AF XY:

0.000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1215150

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

598298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24984

American (AMR)

AF:

0.00

AC:

AN:

13806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19350

East Asian (EAS)

AF:

0.00

AC:

AN:

28324

South Asian (SAS)

AF:

0.000727

AC:

AN:

59128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3614

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

985820

Other (OTH)

AF:

0.0000199

AC:

AN:

50200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000270

AC:

AN:

148320

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41264

American (AMR)

AF:

0.00

AC:

AN:

15054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65444

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000717

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

PhyloP100

0.49

PROVEAN

Benign

0.070

REVEL

Benign

0.091

Sift

Pathogenic

0.0

Sift4G

Benign

0.30

Vest4

0.40

MutPred

0.17

Loss of MoRF binding (P = 0.0305)

MVP

0.099

ClinPred

0.079

GERP RS

3.9

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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