rs3780452

Variant names:

• chr9-98202419-T-C
• rs3780452
• NM_001267571.2:c.2272-755A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267571.2(TBC1D2):​c.2272-755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,050 control chromosomes in the GnomAD database, including 23,712 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23712 hom., cov: 33)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.2272-755A>G		intron_variant	Intron 10 of 12	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.2272-755A>G		intron_variant	Intron 10 of 12	1	NM_001267571.2	ENSP00000481721.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83408 AN: 151930 Hom.: 23689 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.549 AC: 83469 AN: 152050 Hom.: 23712 Cov.: 33 AF XY: 0.548 AC XY: 40693 AN XY: 74320

African (AFR) AF: 0.716 AC: 29681 AN: 41458

American (AMR) AF: 0.494 AC: 7555 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.385 AC: 1990 AN: 5172

South Asian (SAS) AF: 0.517 AC: 2492 AN: 4824

European-Finnish (FIN) AF: 0.485 AC: 5118 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33219 AN: 67980

Other (OTH) AF: 0.533 AC: 1123 AN: 2108

Alfa AF: 0.507 Hom.: 10870

Bravo AF: 0.554

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.29
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3780452; hg19: chr9-100964701;