15-77996195-G-A

Position:

• chr15-77996195-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144572.2(TBC1D2B):​c.*1965C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.13 (0 hom., cov: 30)
  • Exomes 𝑓: 0.17 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D2B NM_144572.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2B	NM_144572.2	c.*1965C>T		3_prime_UTR_variant	13/13	ENST00000300584.8	NP_653173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D2B	ENST00000300584.8	c.*1965C>T		3_prime_UTR_variant	13/13	5	NM_144572.2	ENSP00000300584	P1
TBC1D2B	ENST00000409931.7	c.*2060C>T		3_prime_UTR_variant	13/13	1		ENSP00000387165
TBC1D2B	ENST00000465531.1	c.66+5424C>T		intron_variant		4		ENSP00000453114
TBC1D2B	ENST00000418039.2	n.3187C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 16254 AN: 124976 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.135

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.130 AC: 16257 AN: 125106 Hom.: 0 Cov.: 30 AF XY: 0.131 AC XY: 8086 AN XY: 61782

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.133

Alfa AF: 0.176 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.76

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: rs3825842; hg19: chr15-78288537; COSMIC: COSV56039218; COSMIC: COSV56039218;