rs1674305336

Variant names:

• chr2-39744414-A-T
• rs1674305336
• NM_025264.5:c.1143T>A

Variant summary

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

The NM_001321468.1(THUMPD2):​c.1241T>A​(p.Leu414*) variant causes a stop gained 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: THUMPD2 NM_001321468.1 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321468.1. 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.1143T>A	p.Phe381Leu	missense	Exon 9 of 10	NP_079540.2	Q9BTF0-1
	THUMPD2	NM_001321468.1		c.1241T>A	p.Leu414*	stop_gained	Exon 10 of 11	NP_001308397.1
	THUMPD2	NM_001321474.1		c.1028T>A	p.Leu343*	stop_gained	Exon 8 of 9	NP_001308403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD2	ENST00000505747.6	TSL:1 MANE Select	c.1143T>A	p.Phe381Leu	missense	Exon 9 of 10	ENSP00000423933.1	Q9BTF0-1
	THUMPD2	ENST00000378727.8	TSL:1	n.*352T>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000368001.4	Q9BTF0-2
	THUMPD2	ENST00000460072.5	TSL:1	n.2104T>A		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.39		Loss of methylation at K382 (P = 0.0301)
MVP		0.39
MPC		0.078
ClinPred		0.98	D
GERP RS		0.54
Varity_R		0.32
gMVP		0.54
Mutation Taster		=68/32	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: rs1674305336; hg19: chr2-39971554;