rs10985528

Positions:

• chr9-98228820-A-C

Variant summary

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

The NM_001267571.2(TBC1D2):​c.978+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 799,394 control chromosomes in the GnomAD database, including 3,177 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 0.076 (564 hom., cov: 33)
  • Exomes 𝑓: 0.085 (2613 hom.)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.978+132T>G		intron_variant		ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.978+132T>G		intron_variant		1	NM_001267571.2	ENSP00000481721	P2

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11619 AN: 152150 Hom.: 564 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.0833

GnomAD4 exome AF: 0.0847 AC: 54822 AN: 647126 Hom.: 2613 AF XY: 0.0850 AC XY: 28555 AN XY: 335770

Gnomad4 AFR exome AF: 0.0430

Gnomad4 AMR exome AF: 0.0480

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.000369

Gnomad4 SAS exome AF: 0.0632

Gnomad4 FIN exome AF: 0.0940

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.0877

GnomAD4 genome AF: 0.0764 AC: 11627 AN: 152268 Hom.: 564 Cov.: 33 AF XY: 0.0747 AC XY: 5559 AN XY: 74440

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0634

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.0990

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0922 Hom.: 88

Bravo AF: 0.0708

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.44

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: rs10985528; hg19: chr9-100991102;