chr2-96144874-C-T

Variant names:

• chr2-96144874-C-T
• rs1682478561
• NM_004418.4:c.397G>A

Variant summary

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

The NM_004418.4(DUSP2):​c.397G>A​(p.Asp133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DUSP2 NM_004418.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

DUSP2 (HGNC:3068): (dual specificity phosphatase 2) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1 and ERK2, is predominantly expressed in hematopoietic tissues, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

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=0.16255939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004418.4. 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
	DUSP2	NM_004418.4	MANE Select	c.397G>A	p.Asp133Asn	missense	Exon 2 of 4	NP_004409.1	Q05923

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP2	ENST00000288943.5	TSL:1 MANE Select	c.397G>A	p.Asp133Asn	missense	Exon 2 of 4	ENSP00000288943.4	Q05923
	DUSP2	ENST00000718436.1		c.397G>A	p.Asp133Asn	missense	Exon 2 of 4	ENSP00000520821.1	Q05923
	DUSP2	ENST00000914868.1		c.394G>A	p.Asp132Asn	missense	Exon 2 of 4	ENSP00000584927.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397004 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 688672

African (AFR) AF: 0.00 AC: 0 AN: 31874

American (AMR) AF: 0.00 AC: 0 AN: 35296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24966

East Asian (EAS) AF: 0.00 AC: 0 AN: 36164

South Asian (SAS) AF: 0.00 AC: 0 AN: 79072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077898

Other (OTH) AF: 0.00 AC: 0 AN: 57886

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.032
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.21	T
Polyphen		0.73	P
Vest4		0.20
MutPred		0.40		Gain of methylation at R129 (P = 0.0872)
MVP		0.25
MPC		0.14
ClinPred		0.45	T
GERP RS		1.5
Varity_R		0.17
gMVP		0.26
Mutation Taster		=95/5	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: rs1682478561; hg19: chr2-96810613;