rs2179593

Positions:

• chr20-44031646-C-A
• chr20-44031646-C-G

Variant summary

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

The NM_001098797.2(TOX2):​c.412-19660C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,734 control chromosomes in the GnomAD database, including 38,315 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 0.71 (38315 hom., cov: 29)
• Consequence: TOX2 NM_001098797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

Genes affected

TOX2 (HGNC:16095): (TOX high mobility group box family member 2) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOX2	NM_001098797.2	c.412-19660C>A		intron_variant		ENST00000341197.9	NP_001092267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOX2	ENST00000341197.9	c.412-19660C>A		intron_variant		2	NM_001098797.2	ENSP00000344724.3
TOX2	ENST00000372999.5	c.286-19660C>A		intron_variant		1		ENSP00000362090.1
TOX2	ENST00000358131.5	c.439-19660C>A		intron_variant		2		ENSP00000350849.5
TOX2	ENST00000423191.6	c.286-19660C>A		intron_variant		2		ENSP00000390278.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107376 AN: 151616 Hom.: 38294 Cov.: 29

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.708 AC: 107451 AN: 151734 Hom.: 38315 Cov.: 29 AF XY: 0.708 AC XY: 52522 AN XY: 74132

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.717

Alfa AF: 0.707 Hom.: 19185

Bravo AF: 0.707

Asia WGS AF: 0.675 AC: 2346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.82

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: rs2179593; hg19: chr20-42660286;