rs12352986

Variant names:

• chr9-98223544-T-G
• rs12352986
• NM_001267571.2:c.979-2316A>C

Variant summary

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

The NM_001267571.2(TBC1D2):​c.979-2316A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 152,312 control chromosomes in the GnomAD database, including 740 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 0.084 (740 hom., cov: 33)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.979-2316A>C		intron_variant	Intron 5 of 12	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.979-2316A>C		intron_variant	Intron 5 of 12	1	NM_001267571.2	ENSP00000481721.1

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12765 AN: 152194 Hom.: 740 Cov.: 33

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0941

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

GnomAD4 genome AF: 0.0838 AC: 12759 AN: 152312 Hom.: 740 Cov.: 33 AF XY: 0.0811 AC XY: 6041 AN XY: 74466

African (AFR) AF: 0.0239 AC: 993 AN: 41570

American (AMR) AF: 0.0694 AC: 1061 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0837 AC: 404 AN: 4824

European-Finnish (FIN) AF: 0.0909 AC: 965 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8461 AN: 68024

Other (OTH) AF: 0.0926 AC: 196 AN: 2116

Alfa AF: 0.0980 Hom.: 471

Bravo AF: 0.0773

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.79
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs12352986; hg19: chr9-100985826;