Variant chr15-42745214-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173500.4(TTBK2):c.*581A>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 0.00196 in 156,414 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 1 hom. )

Consequence

TTBK2
NM_173500.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

Variant links:

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]

TTBK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 15-42745214-T-A is Benign according to our data. Variant chr15-42745214-T-A is described in ClinVar as [Benign]. Clinvar id is 315970.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00193 (292/151612) while in subpopulation EAS AF= 0.00503 (26/5172). AF 95% confidence interval is 0.00352. There are 0 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTBK2	NM_173500.4 linkuse as main transcript	c.*581A>T		3_prime_UTR_variant	15/15	ENST00000267890.11	NP_775771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTBK2	ENST00000267890.11 linkuse as main transcript	c.*581A>T		3_prime_UTR_variant	15/15	5	NM_173500.4	ENSP00000267890	P1	Q6IQ55-1

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

292

AN:

151496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00355

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00502

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.0000959

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00434

GnomAD4 exome

AF:

0.00312

AC:

AN:

4802

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

AN XY:

2444

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00578

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00193

AC:

292

AN:

151612

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

134

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.00208

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00503

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.0000959

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.00430

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00209

Asia WGS

AF:

0.00145

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.045

DANN

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over