Genetic Variant NM_001370465.2:c.163C>A (chr2-240560847-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001370465.2(DUSP28):c.163C>A(p.Gln55Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000345 in 1,391,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

DUSP28
NM_001370465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.163C>A	p.Gln55Lys	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
ANKMY1	NM_001308375.4		c.104G>T	p.Cys35Phe	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
DUSP28	NM_001033575.1		c.163C>A	p.Gln55Lys	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.163C>A	p.Gln55Lys	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
ANKMY1	ENST00000403283.6	TSL:1	c.104G>T	p.Cys35Phe	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
ANKMY1	ENST00000464991.5	TSL:1	n.599G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151844

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

30932

AF XY:

0.00

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:

0.0000363

AC:

AN:

1239650

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

607794

show subpopulations

African (AFR)

AF:

0.0000814

AC:

AN:

24570

American (AMR)

AF:

0.00

AC:

AN:

12164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18632

East Asian (EAS)

AF:

0.00

AC:

AN:

27784

South Asian (SAS)

AF:

0.00

AC:

AN:

56272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3570

European-Non Finnish (NFE)

AF:

0.0000424

AC:

AN:

1015156

Other (OTH)

AF:

0.00

AC:

AN:

51040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000198

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67924

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000113

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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.34

PhyloP100

5.6

PROVEAN

Benign

0.32

REVEL

Benign

0.092

Sift

Pathogenic

0.0

Vest4

0.54

MutPred

0.20

Loss of catalytic residue at W36 (P = 0.0015)

MVP

0.43

ClinPred

0.94

GERP RS

3.9

PromoterAI

-0.058

Neutral

(source)

Varity_R

0.69

Mutation Taster

=30/70

disease causing

(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