rs13008299

Positions:

• chr2-29025131-T-G

Variant summary

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

The NM_199280.4(TOGARAM2):​c.1853+757T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,020 control chromosomes in the GnomAD database, including 6,077 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 0.28 (6077 hom., cov: 32)
• Consequence: TOGARAM2 NM_199280.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

Genes affected

TOGARAM2 (HGNC:33715): (TOG array regulator of axonemal microtubules 2) Predicted to enable microtubule binding activity. Predicted to be involved in mitotic spindle assembly. Predicted to be active in cilium and microtubule cytoskeleton. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOGARAM2	NM_199280.4	c.1853+757T>G		intron_variant		ENST00000379558.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOGARAM2	ENST00000379558.5	c.1853+757T>G		intron_variant		5	NM_199280.4	P1
TOGARAM2	ENST00000401723.5	c.158+757T>G		intron_variant		5
TOGARAM2	ENST00000465300.5	n.588+757T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42725 AN: 151902 Hom.: 6069 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.281 AC: 42752 AN: 152020 Hom.: 6077 Cov.: 32 AF XY: 0.278 AC XY: 20653 AN XY: 74308

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.266

Alfa AF: 0.278 Hom.: 1239

Bravo AF: 0.274

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.72

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: rs13008299; hg19: chr2-29247997;