1-205150737-T-C

Variant summary

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

The NM_015375.3(DSTYK):c.2410A>G(p.Met804Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSTYK NM_015375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

DSTYK (HGNC:29043): (dual serine/threonine and tyrosine protein kinase) This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

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	UniProt
DSTYK	NM_015375.3	c.2410A>G	p.Met804Val	missense_variant	11/13	ENST00000367162.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSTYK	ENST00000367162.8	c.2410A>G	p.Met804Val	missense_variant	11/13	1	NM_015375.3	P1
DSTYK	ENST00000367161.7	c.2410A>G	p.Met804Val	missense_variant	11/12	1

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

Oct 17, 2023

The c.2410A>G (p.M804V) alteration is located in exon 11 (coding exon 11) of the DSTYK gene. This alteration results from a A to G substitution at nucleotide position 2410, causing the methionine (M) at amino acid position 804 to be replaced by a valine (V). 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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Pathogenic	26
Dann	Uncertain	0.99
Eigen	Benign	-0.037
Eigen_PC	Benign	0.076
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.28	N;N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0060	D;T
Polyphen		0.74	P;P
Vest4		0.65
MutPred		0.48		Gain of catalytic residue at M804 (P = 0.0714);Gain of catalytic residue at M804 (P = 0.0714);
MVP		0.33
MPC		0.78
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.71
gMVP		0.71

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: chr1-205119865;