rs12352986

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.0909

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.111 Hom.: 251

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12352986; hg19: chr9-100985826;