2-240560847-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

3
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55
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]
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
DUSP28NM_001370465.2 linkc.163C>A p.Gln55Lys missense_variant Exon 1 of 2 ENST00000405954.2 NP_001357394.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DUSP28ENST00000405954.2 linkc.163C>A p.Gln55Lys missense_variant Exon 1 of 2 1 NM_001370465.2 ENSP00000385885.2 Q4G0W2

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151844
Hom.:
0
Cov.:
33
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
GnomAD4 exome
AF:
0.0000363
AC:
45
AN:
1239650
Hom.:
0
Cov.:
30
AF XY:
0.0000362
AC XY:
22
AN XY:
607794
show subpopulations
Gnomad4 AFR exome
AF:
0.0000814
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:
0.0000424
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151844
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74172
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.163C>A (p.Q55K) alteration is located in exon 1 (coding exon 1) of the DUSP28 gene. This alteration results from a C to A substitution at nucleotide position 163, causing the glutamine (Q) at amino acid position 55 to be replaced by a lysine (K). 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
0.73
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
26
DANN
Uncertain
0.98
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.38
T
M_CAP
Pathogenic
0.63
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Uncertain
0.34
D
PROVEAN
Benign
0.32
N
REVEL
Benign
0.092
Sift
Pathogenic
0.0
D
Vest4
0.54
MutPred
0.20
Loss of catalytic residue at W36 (P = 0.0015);
MVP
0.43
ClinPred
0.94
D
GERP RS
3.9

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1047739442; hg19: chr2-241500264; API