NM_001370465.2:c.181C>A

Variant names:

• chr2-240560865-C-A
• rs560521658
• NM_001370465.2:c.181C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370465.2(DUSP28):​c.181C>A​(p.Pro61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,215,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P61S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 0 publications found

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]

ACMG classification

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=0.22113493).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	NM_001370465.2	MANE Select	c.181C>A	p.Pro61Thr	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.86G>T	p.Gly29Val	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.181C>A	p.Pro61Thr	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.181C>A	p.Pro61Thr	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.86G>T	p.Gly29Val	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.581G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215148 Hom.: 0 Cov.: 30 AF XY: 0.00000167 AC XY: 1 AN XY: 598296

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24984

American (AMR) AF: 0.00 AC: 0 AN: 13806

Ashkenazi Jewish (ASJ) AF: 0.0000517 AC: 1 AN: 19350

East Asian (EAS) AF: 0.00 AC: 0 AN: 28324

South Asian (SAS) AF: 0.00 AC: 0 AN: 59128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985820

Other (OTH) AF: 0.00 AC: 0 AN: 50200

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.49
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.18	T
Vest4		0.40
MutPred		0.24		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.19
ClinPred		0.86	D
GERP RS		3.9
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs560521658; hg19: chr2-241500282;