rs757940812

Variant names:

• chr15-78003406-T-C
• NM_144572.2:c.2473A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78003406-T-C
• chr15-78003406-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144572.2(TBC1D2B):​c.2473A>G​(p.Thr825Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T825P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TBC1D2B NM_144572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2B	NM_144572.2	c.2473A>G	p.Thr825Ala	missense_variant	Exon 11 of 13	ENST00000300584.8	NP_653173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D2B	ENST00000300584.8	c.2473A>G	p.Thr825Ala	missense_variant	Exon 11 of 13	5	NM_144572.2	ENSP00000300584.3
TBC1D2B	ENST00000409931.7	c.2473A>G	p.Thr825Ala	missense_variant	Exon 11 of 13	1		ENSP00000387165.3
TBC1D2B	ENST00000472786.1	n.1439A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
TBC1D2B	ENST00000497942.1	n.174A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461604 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.0060
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.028	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		0.83	P;P
Vest4		0.63
MutPred		0.56		Gain of ubiquitination at K821 (P = 0.1162);Gain of ubiquitination at K821 (P = 0.1162);
MVP		0.47
MPC		0.66
ClinPred		0.79	D
GERP RS		5.3
Varity_R		0.22
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-78295748;