15-42745212-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173500.4(TTBK2):c.*583A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 156,920 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (110 hom., cov: 32)
  • Exomes 𝑓: 0.039 (5 hom.)
• Consequence: TTBK2 NM_173500.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

Genes affected

TTBK2 (HGNC:19141): (tau tubulin kinase 2) This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the cerebellum and brainstem. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-42745212-T-A is Benign according to our data. Variant chr15-42745212-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 315969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK2	NM_173500.4	c.*583A>T		3_prime_UTR_variant	15/15	ENST00000267890.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK2	ENST00000267890.11	c.*583A>T		3_prime_UTR_variant	15/15	5	NM_173500.4	P1

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4658 AN: 151950 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0327

GnomAD4 exome AF: 0.0387 AC: 188 AN: 4856 Hom.: 5 Cov.: 0 AF XY: 0.0415 AC XY: 104 AN XY: 2504

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0263

Gnomad4 SAS exome AF: 0.0682

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0429

GnomAD4 genome AF: 0.0306 AC: 4654 AN: 152064 Hom.: 110 Cov.: 32 AF XY: 0.0321 AC XY: 2389 AN XY: 74332

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.0639

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0282 Hom.: 10

Bravo AF: 0.0310

Asia WGS AF: 0.0880 AC: 304 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.6
Dann	Benign	0.52

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: rs116853892; hg19: chr15-43037410;