2-183095590-C-G

Variant names:

• chr2-183095590-C-G
• rs1699790079
• NM_080876.4:c.586C>G

Variant summary

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

The NM_080876.4(DUSP19):​c.586C>G​(p.Gln196Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUSP19 NM_080876.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96
• Publications: 0 publications found

Genes affected

DUSP19 (HGNC:18894): (dual specificity phosphatase 19) Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP19 contains a variation of the consensus DUSP C-terminal catalytic domain, with the last serine residue replaced by alanine, and lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see MIM 600714) (summary by Patterson et al., 2009 [PubMed 19228121]).[supplied by OMIM, Dec 2009]

ENSG00000224643 (HGNC:):

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, 0.957

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080876.4. 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
	DUSP19	NM_080876.4	MANE Select	c.586C>G	p.Gln196Glu	missense	Exon 4 of 4	NP_543152.1	Q8WTR2-1
	DUSP19	NM_001142314.2		c.433C>G	p.Gln145Glu	missense	Exon 3 of 3	NP_001135786.1	Q8WTR2-2
	DUSP19	NM_001321519.2		c.*102C>G		3_prime_UTR	Exon 4 of 4	NP_001308448.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP19	ENST00000354221.5	TSL:1 MANE Select	c.586C>G	p.Gln196Glu	missense	Exon 4 of 4	ENSP00000346160.4	Q8WTR2-1
	DUSP19	ENST00000342619.10	TSL:1	c.433C>G	p.Gln145Glu	missense	Exon 3 of 3	ENSP00000343905.6	Q8WTR2-2
	DUSP19	ENST00000469344.1	TSL:1	n.413C>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.0
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.54
Sift	Benign	0.081	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.88		Gain of glycosylation at S191 (P = 0.1213)
MVP		0.85
MPC		0.39
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.82
Mutation Taster		=22/78	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: rs1699790079; hg19: chr2-183960318;