2-241686678-G-C

Position:

• chr2-241686678-G-C

Variant summary

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

The NM_012145.4(DTYMK):​c.106C>G​(p.Arg36Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DTYMK NM_012145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

Genes affected

DTYMK (HGNC:3061): (deoxythymidylate kinase) Enables thymidylate kinase activity. Predicted to be involved in dTDP biosynthetic process; dTTP biosynthetic process; and dUDP biosynthetic process. Predicted to act upstream of or within cellular response to growth factor stimulus and nucleotide biosynthetic process. Predicted to be located in mitochondrial intermembrane space and mitochondrial matrix. Predicted to be active in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTYMK (HGNC:):

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=0.3748452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTYMK	NM_012145.4	c.106C>G	p.Arg36Gly	missense_variant	1/5	ENST00000305784.7	NP_036277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTYMK	ENST00000305784.7	c.106C>G	p.Arg36Gly	missense_variant	1/5	1	NM_012145.4	ENSP00000304802.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

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

Nov 11, 2024

The c.106C>G (p.R36G) alteration is located in exon 1 (coding exon 1) of the DTYMK gene. This alteration results from a C to G substitution at nucleotide position 106, causing the arginine (R) at amino acid position 36 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.57		Loss of MoRF binding (P = 0.0618);
MVP		0.45
MPC		0.35
ClinPred		0.18	T
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
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

LitVar

Other links and lift over

dbSNP: rs1418297100; hg19: chr2-242626093;