chr2-39764622-C-G

Variant names:

• chr2-39764622-C-G
• rs17024325
• NM_025264.5:c.803+1435G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THUMPD2	NM_025264.5	c.803+1435G>C		intron_variant	Intron 5 of 9	ENST00000505747.6	NP_079540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THUMPD2	ENST00000505747.6	c.803+1435G>C		intron_variant	Intron 5 of 9	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

African (AFR) AF: 0.0822 AC: 3414 AN: 41540

American (AMR) AF: 0.0251 AC: 384 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5194

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4822

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0345 AC: 2346 AN: 68008

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs17024325; hg19: chr2-39991762;