NM_001267571.2:c.978+132T>G

Variant names:

• chr9-98228820-A-C
• rs10985528
• NM_001267571.2:c.978+132T>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.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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D2	NM_001267571.2	c.978+132T>G		intron_variant	Intron 5 of 12	ENST00000465784.7	NP_001254500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7	c.978+132T>G		intron_variant	Intron 5 of 12	1	NM_001267571.2	ENSP00000481721.1

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

African (AFR) AF: 0.0430 AC: 721 AN: 16776

American (AMR) AF: 0.0480 AC: 1220 AN: 25408

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 2386 AN: 14996

East Asian (EAS) AF: 0.000369 AC: 13 AN: 35262

South Asian (SAS) AF: 0.0632 AC: 3207 AN: 50718

European-Finnish (FIN) AF: 0.0940 AC: 3683 AN: 39172

Middle Eastern (MID) AF: 0.0990 AC: 229 AN: 2314

European-Non Finnish (NFE) AF: 0.0942 AC: 40503 AN: 429866

Other (OTH) AF: 0.0877 AC: 2860 AN: 32614

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

African (AFR) AF: 0.0442 AC: 1837 AN: 41562

American (AMR) AF: 0.0552 AC: 844 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 563 AN: 3464

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0634 AC: 306 AN: 4826

European-Finnish (FIN) AF: 0.0868 AC: 921 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0990 AC: 6733 AN: 68004

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0900 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
PhyloP100		1.9
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: rs10985528; hg19: chr9-100991102;