TBC1D2B p.Leu833Leu

Variant names:

• chr15-78003379-C-C
• NM_144572.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-78003380--
• chr15-78003382-G-A
• chr15-78003380-C-A
• chr15-78003380-C-G
• chr15-78003380-C-T
• chr15-78003380-CAG-TAA

Variant summary

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

The NM_144572.2(TBC1D2B):​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: TBC1D2B NM_144572.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D2B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures and gingival overgrowth

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, 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_144572.2. 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
	TBC1D2B	NM_144572.2	MANE Select	c.		exon_region	Exon 11 of 13	NP_653173.1	Q9UPU7-1
	TBC1D2B	NM_001387142.1		c.		exon_region	Exon 11 of 14	NP_001374071.1
	TBC1D2B	NM_001387143.1		c.		exon_region	Exon 11 of 13	NP_001374072.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2B	ENST00000300584.8	TSL:5 MANE Select	c.		exon_region	Exon 11 of 13	ENSP00000300584.3	Q9UPU7-1
	TBC1D2B	ENST00000409931.7	TSL:1	c.		exon_region	Exon 11 of 13	ENSP00000387165.3	Q9UPU7-2
	TBC1D2B	ENST00000936499.1		c.		exon_region	Exon 11 of 13	ENSP00000606558.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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: chr15-78295721;