rs56362282

Variant names:

• chr6-348124-C-A
• rs56362282
• NM_001286555.3:c.285C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-348124-C-A
• chr6-348124-C-G
• chr6-348124-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001286555.3(DUSP22):​c.285C>A​(p.Ser95Arg) 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. Synonymous variant affecting the same amino acid position (i.e. S95S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 61)
• Consequence: DUSP22 NM_001286555.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

Genes affected

DUSP22 (HGNC:16077): (dual specificity phosphatase 22) Enables non-membrane spanning protein tyrosine phosphatase activity and protein tyrosine kinase binding activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; negative regulation of focal adhesion assembly; and negative regulation of non-membrane spanning protein tyrosine kinase activity. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in plasma membrane. Part of cytoplasm; filamentous actin; and leading edge of lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286555.3. 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
	DUSP22	NM_001286555.3	MANE Select	c.285C>A	p.Ser95Arg	missense	Exon 6 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.285C>A	p.Ser95Arg	missense	Exon 6 of 8	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.288C>A		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.285C>A	p.Ser95Arg	missense	Exon 6 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.285C>A	p.Ser95Arg	missense	Exon 6 of 8	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603296.5	TSL:3	c.156C>A	p.Ser52Arg	missense	Exon 6 of 6	ENSP00000474082.1	S4R3A4

Frequencies

GnomAD3 genomes Cov.: 61

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.15	N
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.9	H
PhyloP100		-1.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.95		Gain of MoRF binding (P = 0.0947)
MVP		0.72
MPC		0.36
ClinPred		1.0	D
GERP RS		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		1.0
gMVP		0.94
Mutation Taster		=30/70	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: rs56362282; hg19: chr6-348124;