2-39736945-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025264.5(THUMPD2):​c.1302T>A​(p.Asp434Glu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

THUMPD2
NM_025264.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.474
Variant links:
Genes affected
THUMPD2 (HGNC:14890): (THUMP domain containing 2) Predicted to enable tRNA (guanine) methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.069612145).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THUMPD2NM_025264.5 linkc.1302T>A p.Asp434Glu missense_variant 10/10 ENST00000505747.6 NP_079540.2 Q9BTF0-1Q969Z2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THUMPD2ENST00000505747.6 linkc.1302T>A p.Asp434Glu missense_variant 10/101 NM_025264.5 ENSP00000423933.1 Q9BTF0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 13, 2021The c.1302T>A (p.D434E) alteration is located in exon 10 (coding exon 10) of the THUMPD2 gene. This alteration results from a T to A substitution at nucleotide position 1302, causing the aspartic acid (D) at amino acid position 434 to be replaced by a glutamic acid (E). 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
0.082
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
8.1
DANN
Benign
0.84
DEOGEN2
Benign
0.010
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.11
Sift
Benign
0.47
T
Sift4G
Benign
0.82
T
Polyphen
0.0060
B
Vest4
0.028
MutPred
0.60
Loss of sheet (P = 0.0315);
MVP
0.22
MPC
0.011
ClinPred
0.031
T
GERP RS
-1.1
Varity_R
0.017
gMVP
0.19

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: chr2-39964085; API