2-240560701-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370465.2(DUSP28):​c.17C>T​(p.Ala6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,528,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

DUSP28
NM_001370465.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.193
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0846957).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DUSP28NM_001370465.2 linkc.17C>T p.Ala6Val 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.17C>T p.Ala6Val missense_variant Exon 1 of 2 1 NM_001370465.2 ENSP00000385885.2 Q4G0W2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152138
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000581
AC:
8
AN:
1376724
Hom.:
0
Cov.:
31
AF XY:
0.00000438
AC XY:
3
AN XY:
684792
show subpopulations
Gnomad4 AFR exome
AF:
0.000212
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:
9.24e-7
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152138
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.000265
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.17C>T (p.A6V) 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 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.0097
N
LIST_S2
Benign
0.41
T;.
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.085
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-0.27
N;N
REVEL
Benign
0.074
Sift
Uncertain
0.020
D;D
Sift4G
Benign
0.071
T;T
Polyphen
0.11
B;B
Vest4
0.32
MutPred
0.30
Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP
0.085
MPC
0.33
ClinPred
0.31
T
GERP RS
2.4
Varity_R
0.093
gMVP
0.40

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: rs774218472; hg19: chr2-241500118; API