9-98202369-C-T

Variant names:

• chr9-98202369-C-T
• rs3780453
• NM_001267571.2:c.2272-705G>A

Variant summary

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

The NM_001267571.2(TBC1D2):​c.2272-705G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,970 control chromosomes in the GnomAD database, including 23,616 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 (23616 hom., cov: 32)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.97).
• 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.2272-705G>A		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.2272-705G>A		intron_variant	Intron 10 of 12	1	NM_001267571.2	ENSP00000481721.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83188 AN: 151852 Hom.: 23593 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.548 AC: 83249 AN: 151970 Hom.: 23616 Cov.: 32 AF XY: 0.546 AC XY: 40531 AN XY: 74268

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.530

Alfa AF: 0.490 Hom.: 36960

Bravo AF: 0.554

Asia WGS AF: 0.469 AC: 1629 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.098
DANN	Benign	0.42

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: rs3780453; hg19: chr9-100964651;