15-78003380-CAG-TAA

Variant names:

• chr15-78003380-CAG-TAA
• NM_144572.2:c.2497_2499delCTGinsTTA
• TBC1D2B p.834

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_144572.2(TBC1D2B):​c.2497_2499delCTGinsTTA​(p.834) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L833L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D2B NM_144572.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.2497_2499delCTGinsTTA	p.834	synonymous	N/A	NP_653173.1	Q9UPU7-1
	TBC1D2B	NM_001387142.1		c.2497_2499delCTGinsTTA	p.834	synonymous	N/A	NP_001374071.1
	TBC1D2B	NM_001387143.1		c.2494_2496delCTGinsTTA	p.833	synonymous	N/A	NP_001374072.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2B	ENST00000300584.8	TSL:5 MANE Select	c.2497_2499delCTGinsTTA	p.834	synonymous	N/A	ENSP00000300584.3	Q9UPU7-1
	TBC1D2B	ENST00000409931.7	TSL:1	c.2497_2499delCTGinsTTA	p.834	synonymous	N/A	ENSP00000387165.3	Q9UPU7-2
	TBC1D2B	ENST00000936499.1		c.2500_2502delCTGinsTTA	p.835	synonymous	N/A	ENSP00000606558.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

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: chr15-78295722;