chr17-37512426-G-C

Position:

• chr17-37512426-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007026.4(DUSP14):​c.154G>C​(p.Gly52Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DUSP14 NM_007026.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.16

Genes affected

DUSP14 (HGNC:17007): (dual specificity phosphatase 14) 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. DUSP14 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP14	NM_007026.4	c.154G>C	p.Gly52Arg	missense_variant	3/3	ENST00000617516.5	NP_008957.1
DUSP14	XM_005256977.4	c.154G>C	p.Gly52Arg	missense_variant	3/3		XP_005257034.1
DUSP14	XM_011524234.2	c.154G>C	p.Gly52Arg	missense_variant	3/3		XP_011522536.1
DUSP14	XM_047435217.1	c.154G>C	p.Gly52Arg	missense_variant	3/3		XP_047291173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP14	ENST00000617516.5	c.154G>C	p.Gly52Arg	missense_variant	3/3	1	NM_007026.4	ENSP00000478595.1
DUSP14	ENST00000613659.1	c.154G>C	p.Gly52Arg	missense_variant	3/3	2		ENSP00000484091.1
DUSP14	ENST00000614411.1	c.154G>C	p.Gly52Arg	missense_variant	2/2	2		ENSP00000477653.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Aug 16, 2021

The c.154G>C (p.G52R) alteration is located in exon 3 (coding exon 1) of the DUSP14 gene. This alteration results from a G to C substitution at nucleotide position 154, causing the glycine (G) at amino acid position 52 to be replaced by an arginine (R). 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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.31	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.0040	T
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.85	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.71
MutPred		0.71		Gain of MoRF binding (P = 0.0175);Gain of MoRF binding (P = 0.0175);Gain of MoRF binding (P = 0.0175);
MVP		0.66
ClinPred		0.49	T
GERP RS		5.1
Varity_R		0.49
gMVP		0.80

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: chr17-35872528;