10-133281329-CCG-GCC

Variant names:

• chr10-133281329-CCG-GCC
• NM_006659.4:c.2515_2517delCGGinsGGC
• TUBGCP2 p.Arg839Gly

Variant summary

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

The NM_006659.4(TUBGCP2):​c.2515_2517delCGGinsGGC​(p.Arg839Gly) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R839W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBGCP2 NM_006659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

Genes affected

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 Gene-Disease associations (from GenCC):

• pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006659.4. 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
	TUBGCP2	NM_006659.4	MANE Select	c.2515_2517delCGGinsGGC	p.Arg839Gly	missense	N/A	NP_006650.1	Q9BSJ2-1
	TUBGCP2	NM_001256617.2		c.2599_2601delCGGinsGGC	p.Arg867Gly	missense	N/A	NP_001243546.1	Q9BSJ2-4
	TUBGCP2	NM_001256618.2		c.2125_2127delCGGinsGGC	p.Arg709Gly	missense	N/A	NP_001243547.1	Q9BSJ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP2	ENST00000252936.8	TSL:2 MANE Select	c.2515_2517delCGGinsGGC	p.Arg839Gly	missense	N/A	ENSP00000252936.3	Q9BSJ2-1
	TUBGCP2	ENST00000543663.6	TSL:1	c.2599_2601delCGGinsGGC	p.Arg867Gly	missense	N/A	ENSP00000446093.1	Q9BSJ2-4
	TUBGCP2	ENST00000682161.1		c.2584_2586delCGGinsGGC	p.Arg862Gly	missense	N/A	ENSP00000507509.1	A0A804HJH7

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

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: chr10-135094833;