Genetic Variant DUSP28:p.Ala41Gly (chr2-240560806-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370465.2(DUSP28):c.122C>G(p.Ala41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

DUSP28
NM_001370465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.572

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24405497).

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.122C>G	p.Ala41Gly	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
ANKMY1	NM_001308375.4		c.145G>C	p.Ala49Pro	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
DUSP28	NM_001033575.1		c.122C>G	p.Ala41Gly	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.122C>G	p.Ala41Gly	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
ANKMY1	ENST00000403283.6	TSL:1	c.145G>C	p.Ala49Pro	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
ANKMY1	ENST00000464991.5	TSL:1	n.640G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151924

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.75e-7

AC:

AN:

1289892

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

634966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26130

American (AMR)

AF:

0.00

AC:

AN:

19710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21422

East Asian (EAS)

AF:

0.00

AC:

AN:

28394

South Asian (SAS)

AF:

0.00

AC:

AN:

67238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3930

European-Non Finnish (NFE)

AF:

9.64e-7

AC:

AN:

1037568

Other (OTH)

AF:

0.00

AC:

AN:

53242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00000658

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

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

0.079

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.4

(source)

DANN

Benign

0.75

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.52

M_CAP

Benign

0.032

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PhyloP100

-0.57

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.093

Sift

Benign

0.24

Sift4G

Benign

0.36

Polyphen

0.71

Vest4

0.17

MutPred

0.45

Loss of stability (P = 0.0567)

MVP

0.43

MPC

0.65

ClinPred

0.68

GERP RS

-0.70

PromoterAI

-0.059

Neutral

(source)

Varity_R

0.18

gMVP

0.26

Mutation Taster

=83/17

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