rs371626516

Variant names:

• chr9-98201589-C-A
• rs371626516
• NM_001267571.2:c.2347G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-98201589-C-A
• chr9-98201589-C-T

Variant summary

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

The NM_001267571.2(TBC1D2):​c.2347G>T​(p.Val783Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V783M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D2 NM_001267571.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.2347G>T	p.Val783Leu	missense_variant	Exon 11 of 13	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.2347G>T	p.Val783Leu	missense_variant	Exon 11 of 13	1	NM_001267571.2	ENSP00000481721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T;.;.;.;.
Eigen	Benign	0.00052
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.84	T;T;D;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;L;.;L
PhyloP100		0.30
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	.;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	.;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D
Polyphen		0.96	D;.;.;.;P
Vest4		0.60
MutPred		0.72		Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);
MVP		0.52
MPC		0.59
ClinPred		0.74	D
GERP RS		2.7
Varity_R		0.052
gMVP		0.39
Mutation Taster		=89/11	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: rs371626516; hg19: chr9-100963871;