chr9-98226195-G-A

Variant names:

• chr9-98226195-G-A
• rs16914086
• NM_001267571.2:c.978+2757C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267571.2(TBC1D2):​c.978+2757C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,184 control chromosomes in the GnomAD database, including 984 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 0.099 (984 hom., cov: 33)
• Consequence: TBC1D2 NM_001267571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267571.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2	NM_001267571.2	MANE Select	c.978+2757C>T		intron	N/A	NP_001254500.1
	TBC1D2	NM_018421.4		c.978+2757C>T		intron	N/A	NP_060891.3
	TBC1D2	NM_001410988.1		c.978+2757C>T		intron	N/A	NP_001397917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2	ENST00000465784.7	TSL:1 MANE Select	c.978+2757C>T		intron	N/A	ENSP00000481721.1
	TBC1D2	ENST00000375066.6	TSL:1	c.978+2757C>T		intron	N/A	ENSP00000364207.5
	TBC1D2	ENST00000375064.5	TSL:1	c.978+2757C>T		intron	N/A	ENSP00000364205.1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15053 AN: 152064 Hom.: 984 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.0989 AC: 15058 AN: 152184 Hom.: 984 Cov.: 33 AF XY: 0.103 AC XY: 7659 AN XY: 74392

African (AFR) AF: 0.0257 AC: 1066 AN: 41542

American (AMR) AF: 0.150 AC: 2295 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.112 AC: 579 AN: 5172

South Asian (SAS) AF: 0.118 AC: 571 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1779 AN: 10572

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8229 AN: 68006

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.106 Hom.: 2047

Bravo AF: 0.0934

Asia WGS AF: 0.123 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.51
PhyloP100		-0.62
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: rs16914086; hg19: chr9-100988477;