2-240560847-C-G

Variant names:

• chr2-240560847-C-G
• rs1047739442
• NM_001370465.2:c.163C>G

Variant summary

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

The NM_001370465.2(DUSP28):​c.163C>G​(p.Gln55Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Q55K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	NM_001370465.2	MANE Select	c.163C>G	p.Gln55Glu	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.104G>C	p.Cys35Ser	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.163C>G	p.Gln55Glu	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.163C>G	p.Gln55Glu	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.104G>C	p.Cys35Ser	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.599G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1239652 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 607796

African (AFR) AF: 0.00 AC: 0 AN: 24570

American (AMR) AF: 0.00 AC: 0 AN: 12164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18632

East Asian (EAS) AF: 0.00 AC: 0 AN: 27784

South Asian (SAS) AF: 0.00 AC: 0 AN: 56274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3570

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1015156

Other (OTH) AF: 0.00 AC: 0 AN: 51040

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.34	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.26	D
PhyloP100		5.6
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D
Vest4		0.53
MutPred		0.21		Loss of catalytic residue at W36 (P = 7e-04)
MVP		0.37
ClinPred		0.91	D
GERP RS		3.9
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1047739442; hg19: chr2-241500264;