rs2900463

chr9-98215175-T-C

Variant summary

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

The NM_001267571.2(TBC1D2):c.1375-1957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,084 control chromosomes in the GnomAD database, including 30,043 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 0.62 (30043 hom., cov: 32)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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 = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D2	NM_001267571.2	c.1375-1957A>G		intron_variant		ENST00000465784.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D2	ENST00000465784.7	c.1375-1957A>G		intron_variant		1	NM_001267571.2	P2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94426 AN: 151966 Hom.: 30004 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.621 AC: 94508 AN: 152084 Hom.: 30043 Cov.: 32 AF XY: 0.619 AC XY: 46032 AN XY: 74342

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.613

Alfa AF: 0.604 Hom.: 4449

Bravo AF: 0.628

Asia WGS AF: 0.568 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.035
Dann	Benign	0.48

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: rs2900463; hg19: chr9-100977457;