chr14-31457357-G-A

Position:

• chr14-31457357-G-A

Variant summary

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

The NM_080664.3(DTD2):​c.37C>T​(p.Leu13Phe) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DTD2 NM_080664.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49

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]

(HGNC:):

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
DTD2	NM_080664.3	c.37C>T	p.Leu13Phe	missense_variant	1/3	ENST00000310850.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTD2	ENST00000310850.9	c.37C>T	p.Leu13Phe	missense_variant	1/3	1	NM_080664.3	P1
DTD2	ENST00000549850.1	c.37C>T	p.Leu13Phe	missense_variant, NMD_transcript_variant	1/3	2
	ENST00000547760.1	c.22C>T	p.Leu8Phe	missense_variant, NMD_transcript_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1435690 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 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

May 08, 2024

The c.37C>T (p.L13F) alteration is located in exon 1 (coding exon 1) of the DTD2 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a phenylalanine (F). 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	0.56
BayesDel_addAF	Benign	-0.0088	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.0	.;M;M
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.55
MutPred		0.64		Gain of catalytic residue at L18 (P = 0);Gain of catalytic residue at L18 (P = 0);Gain of catalytic residue at L18 (P = 0);
MVP		0.68
MPC		1.1
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.28
gMVP		0.57

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: chr14-31926563;