rs7868451

Positions:

• chr9-98225340-A-G
• chr9-98225340-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267571.2(TBC1D2):​c.978+3612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,142 control chromosomes in the GnomAD database, including 17,846 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 0.44 (17846 hom., cov: 32)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D2	NM_001267571.2	c.978+3612T>C		intron_variant		ENST00000465784.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D2	ENST00000465784.7	c.978+3612T>C		intron_variant		1	NM_001267571.2	P2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67170 AN: 152024 Hom.: 17819 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.442 AC: 67246 AN: 152142 Hom.: 17846 Cov.: 32 AF XY: 0.435 AC XY: 32349 AN XY: 74368

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.410

Alfa AF: 0.330 Hom.: 11378

Bravo AF: 0.456

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.83

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: rs7868451; hg19: chr9-100987622;