rs192033192

Variant names:

• chr9-98199448-C-G
• rs192033192
• NM_001267571.2:c.2720G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-98199448-C-G
• chr9-98199448-C-T

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.2720G>C​(p.Arg907Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. R907Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TBC1D2 NM_001267571.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• 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=0.2401545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.2720G>C	p.Arg907Pro	missense_variant	Exon 13 of 13	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.2720G>C	p.Arg907Pro	missense_variant	Exon 13 of 13	1	NM_001267571.2	ENSP00000481721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T;.;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PhyloP100		-0.092
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.4	.;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	.;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.91	P;.;.;P
Vest4		0.31
MutPred		0.38		Gain of loop (P = 3e-04);.;.;.;
MVP		0.50
MPC		1.1
ClinPred		0.95	D
GERP RS		0.40
Varity_R		0.22
gMVP		0.71
Mutation Taster		=80/20	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

dbSNP: rs192033192; hg19: chr9-100961730;