chr15-42746172-G-G

Variant names:

• chr15-42746172-G-G
• NM_173500.4:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173500.4(TTBK2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTBK2 NM_173500.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 11

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173500.4. 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
	TTBK2	NM_173500.4	MANE Select	c.		exon_region	Exon 15 of 15	NP_775771.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTBK2	ENST00000267890.11	TSL:5 MANE Select	c.		exon_region	Exon 15 of 15	ENSP00000267890.6	Q6IQ55-1
	TTBK2	ENST00000903061.1		c.		exon_region	Exon 15 of 15	ENSP00000573120.1
	TTBK2	ENST00000903062.1		c.		exon_region	Exon 14 of 14	ENSP00000573121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-43038370;