2-183083525-C-T

Variant names:

• chr2-183083525-C-T
• rs777582682
• NM_080876.4:c.244C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080876.4(DUSP19):​c.244C>T​(p.His82Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,610,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. H82N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DUSP19 NM_080876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23566097).

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.244C>T	p.His82Tyr	missense	Exon 2 of 4	NP_543152.1	Q8WTR2-1
	DUSP19	NM_001142314.2		c.244C>T	p.His82Tyr	missense	Exon 2 of 3	NP_001135786.1	Q8WTR2-2
	DUSP19	NM_001321519.2		c.244C>T	p.His82Tyr	missense	Exon 2 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.244C>T	p.His82Tyr	missense	Exon 2 of 4	ENSP00000346160.4	Q8WTR2-1
	DUSP19	ENST00000342619.10	TSL:1	c.244C>T	p.His82Tyr	missense	Exon 2 of 3	ENSP00000343905.6	Q8WTR2-2
	DUSP19	ENST00000469344.1	TSL:1	n.189C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151922 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250112 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459026 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725736

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 85630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110522

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151922 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74152

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.097
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.44	T
Sift4G	Benign	0.69	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.45		Loss of disorder (P = 0.0342)
MVP		0.58
MPC		0.082
ClinPred		0.60	D
GERP RS		5.2
Varity_R		0.73
gMVP		0.76
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777582682; hg19: chr2-183948253;