2-39737006-C-T

Variant names:

• chr2-39737006-C-T
• rs1186639494
• NM_025264.5:c.1241G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025264.5(THUMPD2):​c.1241G>A​(p.Arg414Lys) 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. 16/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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]

LOC124905994 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08202103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD2	NM_025264.5	MANE Select	c.1241G>A	p.Arg414Lys	missense	Exon 10 of 10	NP_079540.2	Q9BTF0-1
	THUMPD2	NM_001321469.1		c.962G>A	p.Arg321Lys	missense	Exon 10 of 10	NP_001308398.1
	THUMPD2	NM_001321470.1		c.914G>A	p.Arg305Lys	missense	Exon 10 of 10	NP_001308399.1	B4DP37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD2	ENST00000505747.6	TSL:1 MANE Select	c.1241G>A	p.Arg414Lys	missense	Exon 10 of 10	ENSP00000423933.1	Q9BTF0-1
	THUMPD2	ENST00000378727.8	TSL:1	n.*450G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000368001.4	Q9BTF0-2
	THUMPD2	ENST00000460072.5	TSL:1	n.2202G>A		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.7
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.059
Sift	Benign	0.36	T
Sift4G	Benign	0.53	T
Polyphen		0.0060	B
Vest4		0.067
MutPred		0.68		Gain of ubiquitination at R414 (P = 0.0203)
MVP		0.28
MPC		0.011
ClinPred		0.13	T
GERP RS		4.0
Varity_R		0.059
gMVP		0.26
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1186639494; hg19: chr2-39964146;