ENST00000401723.5:c.-147+839A>G

Variant names:

• chr2-28957536-A-G
• rs13402702
• ENST00000401723.5:c.-147+839A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000401723.5(TOGARAM2):​c.-147+839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,202 control chromosomes in the GnomAD database, including 1,557 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 0.12 (1557 hom., cov: 32)
• Consequence: TOGARAM2 ENST00000401723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOGARAM2	XM_047443568.1	c.-111+839A>G		intron_variant	Intron 1 of 19		XP_047299524.1
TOGARAM2	XM_047443570.1	c.-111+839A>G		intron_variant	Intron 1 of 16		XP_047299526.1
TOGARAM2	XM_047443574.1	c.-127+839A>G		intron_variant	Intron 1 of 15		XP_047299530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOGARAM2	ENST00000401723.5	c.-147+839A>G		intron_variant	Intron 1 of 6	5		ENSP00000384897.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18721 AN: 152084 Hom.: 1555 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.123 AC: 18723 AN: 152202 Hom.: 1557 Cov.: 32 AF XY: 0.121 AC XY: 9017 AN XY: 74414

African (AFR) AF: 0.0310 AC: 1288 AN: 41546

American (AMR) AF: 0.119 AC: 1815 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0568 AC: 274 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12567 AN: 68002

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.164 Hom.: 4139

Bravo AF: 0.115

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13402702; hg19: chr2-29180402;