rs17024325

Positions:

• chr2-39764622-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025264.5(THUMPD2):​c.803+1435G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,270 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (214 hom., cov: 33)
• Consequence: THUMPD2 NM_025264.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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]

THUMPD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THUMPD2	NM_025264.5	c.803+1435G>C		intron_variant		ENST00000505747.6	NP_079540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THUMPD2	ENST00000505747.6	c.803+1435G>C		intron_variant		1	NM_025264.5	ENSP00000423933.1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6763 AN: 152152 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0446 AC: 6794 AN: 152270 Hom.: 214 Cov.: 33 AF XY: 0.0429 AC XY: 3194 AN XY: 74454

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0415 Hom.: 27

Bravo AF: 0.0464

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs17024325; hg19: chr2-39991762;