rs13008299

Variant names:

• chr2-29025131-T-G
• rs13008299
• NM_199280.4:c.1853+757T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

TOGARAM2 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199280.4. 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
	TOGARAM2	NM_199280.4	MANE Select	c.1853+757T>G		intron	N/A	NP_954974.2	Q6ZUX3-1
	TOGARAM2	NM_001321538.3		c.1688+757T>G		intron	N/A	NP_001308467.1
	TOGARAM2	NM_001321539.3		c.1280+757T>G		intron	N/A	NP_001308468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM2	ENST00000379558.5	TSL:5 MANE Select	c.1853+757T>G		intron	N/A	ENSP00000368876.3	Q6ZUX3-1
	TOGARAM2	ENST00000956354.1		c.1853+757T>G		intron	N/A	ENSP00000626413.1
	TOGARAM2	ENST00000929817.1		c.1853+757T>G		intron	N/A	ENSP00000599876.1

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

African (AFR) AF: 0.292 AC: 12112 AN: 41466

American (AMR) AF: 0.225 AC: 3433 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1132 AN: 3464

East Asian (EAS) AF: 0.169 AC: 870 AN: 5162

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4816

European-Finnish (FIN) AF: 0.321 AC: 3388 AN: 10570

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19637 AN: 67958

Other (OTH) AF: 0.266 AC: 562 AN: 2112

Alfa AF: 0.280 Hom.: 2866

Bravo AF: 0.274

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		0.34
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: rs13008299; hg19: chr2-29247997;