chr9-98199463-T-C

Variant names:

• chr9-98199463-T-C
• NM_001267571.2:c.2705A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001267571.2(TBC1D2):​c.2705A>G​(p.Glu902Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D2 NM_001267571.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

TBC1D2 (HGNC:18026): (TBC1 domain family member 2) Enables GTPase activator activity and cadherin binding activity. Involved in positive regulation of GTPase activity. Located in several cellular components, including cytoplasmic vesicle; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299446 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13427177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267571.2. 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
	TBC1D2	NM_001267571.2	MANE Select	c.2705A>G	p.Glu902Gly	missense	Exon 13 of 13	NP_001254500.1	Q9BYX2-1
	TBC1D2	NM_018421.4		c.2672A>G	p.Glu891Gly	missense	Exon 13 of 13	NP_060891.3	Q9BYX2-2
	TBC1D2	NM_001267572.1		c.1325A>G	p.Glu442Gly	missense	Exon 7 of 7	NP_001254501.1	Q9BYX2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2	ENST00000465784.7	TSL:1 MANE Select	c.2705A>G	p.Glu902Gly	missense	Exon 13 of 13	ENSP00000481721.1	Q9BYX2-1
	TBC1D2	ENST00000375066.6	TSL:1	c.2672A>G	p.Glu891Gly	missense	Exon 13 of 13	ENSP00000364207.5	Q9BYX2-2
	TBC1D2	ENST00000375063.5	TSL:1	c.1325A>G	p.Glu442Gly	missense	Exon 7 of 7	ENSP00000364203.1	Q9BYX2-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.042
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.22	B
Vest4		0.11
MutPred		0.34		Loss of stability (P = 0.016)
MVP		0.54
MPC		0.68
ClinPred		0.74	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.42
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr9-100961745;