2-73780060-C-T

Position:

• chr2-73780060-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001424649.1(DUSP11):​c.56G>A​(p.Cys19Tyr) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: DUSP11 NM_001424649.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00600

Genes affected

DUSP11 (HGNC:3066): (dual specificity phosphatase 11) 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 is 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 is localized to the nucleus and binds directly to RNA and splicing factors, and thus it is suggested to participate in nuclear mRNA metabolism. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06859067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP11	NM_003584.3	c.-86G>A		5_prime_UTR_variant	1/9	ENST00000272444.8	NP_003575.3
DUSP11	NM_001424649.1	c.56G>A	p.Cys19Tyr	missense_variant	1/9		NP_001411578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP11	ENST00000272444.8	c.-86G>A		5_prime_UTR_variant	1/9	1	NM_003584.3	ENSP00000272444.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.56G>A (p.C19Y) alteration is located in exon 1 (coding exon 1) of the DUSP11 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the cysteine (C) at amino acid position 19 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.83
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.027
Sift	Benign	0.067	T;D
Sift4G	Benign	0.14	T;D
Vest4		0.14
MutPred		0.53		Loss of catalytic residue at L20 (P = 0.0397);Loss of catalytic residue at L20 (P = 0.0397);
MVP		0.092
MPC		0.51
ClinPred		0.070	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74007187;