chr22-30663802-G-C

Position:

• chr22-30663802-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152511.5(DUSP18):​c.202C>G​(p.Gln68Glu) 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. 15/21 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)
• Consequence: DUSP18 NM_152511.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39

Genes affected

DUSP18 (HGNC:18484): (dual specificity phosphatase 18) 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. DUSP18 contains the consensus DUSP C-terminal catalytic domain but 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]

SLC35E4 (HGNC:17058): (solute carrier family 35 member E4) Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3025115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP18	NM_152511.5	c.202C>G	p.Gln68Glu	missense_variant	2/2	ENST00000334679.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP18	ENST00000334679.4	c.202C>G	p.Gln68Glu	missense_variant	2/2	1	NM_152511.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 08, 2022

The c.202C>G (p.Q68E) alteration is located in exon 2 (coding exon 1) of the DUSP18 gene. This alteration results from a C to G substitution at nucleotide position 202, causing the glutamine (Q) at amino acid position 68 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T;T;T;.
Eigen	Benign	-0.047
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M;M;M;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.030	D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.098	B;B;B;.
Vest4		0.21
MutPred		0.47		Gain of disorder (P = 0.2168);Gain of disorder (P = 0.2168);Gain of disorder (P = 0.2168);Gain of disorder (P = 0.2168);
MVP		0.72
MPC		0.048
ClinPred		0.27	T
GERP RS		5.2
Varity_R		0.31
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-31059789;