2-183095537-C-T

Variant names:

• chr2-183095537-C-T
• rs1003374103
• NM_080876.4:c.533C>T

Variant summary

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

The NM_080876.4(DUSP19):​c.533C>T​(p.Ser178Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,460,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: DUSP19 NM_080876.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• 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: 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_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.533C>T	p.Ser178Phe	missense	Exon 4 of 4	NP_543152.1	Q8WTR2-1
	DUSP19	NM_001142314.2		c.380C>T	p.Ser127Phe	missense	Exon 3 of 3	NP_001135786.1	Q8WTR2-2
	DUSP19	NM_001321519.2		c.*49C>T		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.533C>T	p.Ser178Phe	missense	Exon 4 of 4	ENSP00000346160.4	Q8WTR2-1
	DUSP19	ENST00000342619.10	TSL:1	c.380C>T	p.Ser127Phe	missense	Exon 3 of 3	ENSP00000343905.6	Q8WTR2-2
	DUSP19	ENST00000469344.1	TSL:1	n.360C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251402 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000308 AC: 45 AN: 1460490 Hom.: 0 Cov.: 33 AF XY: 0.0000317 AC XY: 23 AN XY: 726588

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111248

Other (OTH) AF: 0.0000497 AC: 3 AN: 60302

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.2
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.83	P
Vest4		0.47
MutPred		0.52		Loss of disorder (P = 0.0244)
MVP		0.94
MPC		0.19
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.79
gMVP		0.51
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: rs1003374103; hg19: chr2-183960265;