NM_001370465.2:c.266T>G

Variant names:

• chr2-240560950-T-G
• rs1354648614
• NM_001370465.2:c.266T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370465.2(DUSP28):​c.266T>G​(p.Met89Arg) variant causes a missense change. 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. M89I) 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: 3.63
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

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.266T>G	p.Met89Arg	missense	Exon 1 of 2	NP_001357394.1	Q4G0W2
	DUSP28	NM_001033575.1		c.266T>G	p.Met89Arg	missense	Exon 1 of 3	NP_001028747.1	Q4G0W2
	ANKMY1	NM_001308375.4		c.1A>C	p.Met1?	initiator_codon	Exon 1 of 15	NP_001295304.3	J3KPY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP28	ENST00000405954.2	TSL:1 MANE Select	c.266T>G	p.Met89Arg	missense	Exon 1 of 2	ENSP00000385885.2	Q4G0W2
	ANKMY1	ENST00000403283.6	TSL:1	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 15	ENSP00000383968.1	J3KPY5
	ANKMY1	ENST00000464991.5	TSL:1	n.496A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	29
DANN	Uncertain	0.98
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.79	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.027	T
PhyloP100		3.6
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Vest4		0.68
MutPred		0.74		Loss of sheet (P = 0.0817)
MVP		0.32
ClinPred		1.0	D
GERP RS		2.5
PromoterAI		-0.26	Neutral
Varity_R		0.99
Mutation Taster		=77/123	disease causing

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: rs1354648614; hg19: chr2-241500367;