14-31448332-T-C

Position:

• chr14-31448332-T-C

Variant summary

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

The NM_080664.3(DTD2):​c.304A>G​(p.Arg102Gly) variant causes a missense change involving the alteration of a non-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: DTD2 NM_080664.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

DTD2 (HGNC:20277): (D-aminoacyl-tRNA deacylase 2) Enables Ala-tRNA(Thr) hydrolase activity. Involved in aminoacyl-tRNA metabolism involved in translational fidelity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000203546 (HGNC:):

HEATR5A-DT (HGNC:55552): (HEATR5A divergent transcript)

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
DTD2	NM_080664.3	c.304A>G	p.Arg102Gly	missense_variant	3/3	ENST00000310850.9	NP_542395.1
HEATR5A-DT	NR_110045.1	n.436+2598T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD2	ENST00000310850.9	c.304A>G	p.Arg102Gly	missense_variant	3/3	1	NM_080664.3	ENSP00000312224.4
ENSG00000203546	ENST00000547378.1	c.181+4943A>G		intron_variant		3		ENSP00000447056.1
ENSG00000203546	ENST00000547760.1	n.*228+4943A>G		intron_variant		3		ENSP00000449799.1

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

Sep 30, 2024

The c.304A>G (p.R102G) alteration is located in exon 3 (coding exon 3) of the DTD2 gene. This alteration results from a A to G substitution at nucleotide position 304, causing the arginine (R) at amino acid position 102 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	0.27
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.097	T;T
Polyphen		0.93	P;P
Vest4		0.50
MutPred		0.65		Gain of catalytic residue at K100 (P = 0);Gain of catalytic residue at K100 (P = 0);
MVP		0.74
MPC		0.53
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.69
gMVP		0.64

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: chr14-31917538;