Genetic Variant NM_144572.2:c.*1965C>T (chr15-77996195-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

Publications

2 publications found

Variant links:

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]

TBC1D2B Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures and gingival overgrowth
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

TBC1D2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2B	NM_144572.2 link	c.*1965C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000300584.8	NP_653173.1	Q9UPU7-1B2RTQ2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D2B	ENST00000300584.8 link	c.*1965C>T	3_prime_UTR_variant	Exon 13 of 13	5	NM_144572.2	ENSP00000300584.3	Q9UPU7-1
TBC1D2B	ENST00000409931.7 link	c.*2060C>T	3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000387165.3	Q9UPU7-2
TBC1D2B	ENST00000418039.2 link	n.3187C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
TBC1D2B	ENST00000465531.1 link	c.64+5424C>T	intron_variant	Intron 1 of 1	4		ENSP00000453114.1	H0YL97

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

16254

AN:

124976

Hom.:

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.130

AC:

16257

AN:

125106

Hom.:

Cov.:

AF XY:

0.131

AC XY:

8086

AN XY:

61782

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0468

AC:

1731

AN:

37010

American (AMR)

AF:

0.102

AC:

1330

AN:

13038

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

438

AN:

2680

East Asian (EAS)

AF:

0.0469

AC:

220

AN:

4692

South Asian (SAS)

AF:

0.135

AC:

509

AN:

3778

European-Finnish (FIN)

AF:

0.160

AC:

1395

AN:

8718

Middle Eastern (MID)

AF:

0.106

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.195

AC:

10223

AN:

52518

Other (OTH)

AF:

0.133

AC:

230

AN:

1730

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

Heterozygous variant carriers

1223

2446

3669

4892

6115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.176

Hom.:

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

(source)

DANN

Benign

0.76

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over