20-31861462-G-T

Position:

• chr20-31861462-G-T

Variant summary

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

The NM_080611.5(DUSP15):​c.649C>A​(p.Arg217Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,400,742 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DUSP15 NM_080611.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

Genes affected

DUSP15 (HGNC:16236): (dual specificity phosphatase 15) The protein encoded by this gene has both protein-tyrosine phophatase activity and serine/threonine-specific phosphatase activity, and therefore is known as a dual specificity phosphatase. This protein may function in the differentiation of oligodendrocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP15	NM_080611.5	c.649C>A	p.Arg217Ser	missense_variant	7/7	ENST00000339738.10	NP_542178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP15	ENST00000339738.10	c.649C>A	p.Arg217Ser	missense_variant	7/7	1	NM_080611.5	ENSP00000341658.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000191 AC: 3 AN: 156672 Hom.: 0 AF XY: 0.0000229 AC XY: 2 AN XY: 87428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000214 AC: 3 AN: 1400742 Hom.: 0 Cov.: 40 AF XY: 0.00000288 AC XY: 2 AN XY: 693924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000789

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 15, 2024

The c.649C>A (p.R217S) alteration is located in exon 7 (coding exon 7) of the DUSP15 gene. This alteration results from a C to A substitution at nucleotide position 649, causing the arginine (R) at amino acid position 217 to be replaced by a serine (S). 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
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	30
DANN	Uncertain	1.0
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	T;.;.;T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.35	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.85	N;N;N;N;N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;.;.;.;D
Vest4		0.60
MutPred		0.30		.;.;.;.;Loss of MoRF binding (P = 0.0061);
MVP		0.66
MPC		0.58
ClinPred		0.88	D
GERP RS		4.0

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

LitVar

Other links and lift over

dbSNP: rs1208365679; hg19: chr20-30449265;