2-240560913-G-C

Variant names:

• chr2-240560913-G-C
• rs756613284
• NM_001370465.2:c.229G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370465.2(DUSP28):​c.229G>C​(p.Asp77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D77N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUSP28 NM_001370465.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

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.229G>C	p.Asp77His	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.38C>G	p.Ser13Cys	missense	Exon 1 of 15	NP_001295304.3	J3KPY5
	DUSP28	NM_001033575.1		c.229G>C	p.Asp77His	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.229G>C	p.Asp77His	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.38C>G	p.Ser13Cys	missense	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.533C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.70	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.41
Sift	Benign	0.55	T
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.50		Gain of catalytic residue at L79 (P = 0.0821)
MVP		0.68
MPC		1.2
ClinPred		0.99	D
GERP RS		3.0
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.48
gMVP		0.68
Mutation Taster		=55/45	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: rs756613284; hg19: chr2-241500330;