rs2900463

Variant names:

• chr9-98215175-T-C
• rs2900463
• NM_001267571.2:c.1375-1957A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ENSG00000299446 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.1375-1957A>G		intron_variant	Intron 6 of 12	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.1375-1957A>G		intron_variant	Intron 6 of 12	1	NM_001267571.2	ENSP00000481721.1

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

African (AFR) AF: 0.764 AC: 31684 AN: 41486

American (AMR) AF: 0.568 AC: 8681 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2746 AN: 5164

South Asian (SAS) AF: 0.542 AC: 2615 AN: 4824

European-Finnish (FIN) AF: 0.555 AC: 5871 AN: 10574

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.572 AC: 38869 AN: 67976

Other (OTH) AF: 0.613 AC: 1290 AN: 2106

Alfa AF: 0.607 Hom.: 4656

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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2900463; hg19: chr9-100977457;