2-240560865-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 11/17 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

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04337555).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DUSP28NM_001370465.2 linkc.181C>T p.Pro61Ser 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.181C>T p.Pro61Ser missense_variant Exon 1 of 2 1 NM_001370465.2 ENSP00000385885.2 Q4G0W2

Frequencies

GnomAD3 genomes
AF:
0.0000270
AC:
4
AN:
148210
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:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000132
AC:
7
AN:
53172
Hom.:
0
AF XY:
0.000154
AC XY:
5
AN XY:
32474
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 SAS exome
AF:
0.000742
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000379
AC:
46
AN:
1215150
Hom.:
0
Cov.:
30
AF XY:
0.0000518
AC XY:
31
AN XY:
598298
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000727
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000203
Gnomad4 OTH exome
AF:
0.0000199
GnomAD4 genome
AF:
0.0000270
AC:
4
AN:
148320
Hom.:
0
Cov.:
33
AF XY:
0.0000276
AC XY:
2
AN XY:
72528
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:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000717
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.181C>T (p.P61S) alteration is located in exon 1 (coding exon 1) of the DUSP28 gene. This alteration results from a C to T substitution at nucleotide position 181, causing the proline (P) at amino acid position 61 to be replaced by a serine (S). 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
Benign
0.10
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Uncertain
0.98
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.38
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.070
N
REVEL
Benign
0.091
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.30
T
Vest4
0.40
MutPred
0.17
Loss of MoRF binding (P = 0.0305);
MVP
0.099
ClinPred
0.079
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs560521658; hg19: chr2-241500282; API