NM_001267571.2:c.2440C>T

Variant names:

• chr9-98201496-G-A
• rs147981592
• NM_001267571.2:c.2440C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001267571.2(TBC1D2):​c.2440C>T​(p.Leu814Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00442 in 1,614,020 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: TBC1D2 NM_001267571.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.55
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-98201496-G-A is Benign according to our data. Variant chr9-98201496-G-A is described in ClinVar as Benign. ClinVar VariationId is 712999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.55 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 24 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2	NM_001267571.2	MANE Select	c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	NP_001254500.1	Q9BYX2-1
	TBC1D2	NM_018421.4		c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	NP_060891.3	Q9BYX2-2
	TBC1D2	NM_001410988.1		c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	NP_001397917.1	Q9BYX2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D2	ENST00000465784.7	TSL:1 MANE Select	c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	ENSP00000481721.1	Q9BYX2-1
	TBC1D2	ENST00000375066.6	TSL:1	c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	ENSP00000364207.5	Q9BYX2-2
	TBC1D2	ENST00000375064.5	TSL:1	c.2440C>T	p.Leu814Leu	synonymous	Exon 11 of 13	ENSP00000364205.1	Q9BYX2-3

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 422 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00257 AC: 645 AN: 251146 AF XY: 0.00272

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00227

Gnomad NFE exome AF: 0.00411

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00460 AC: 6720 AN: 1461724 Hom.: 24 Cov.: 31 AF XY: 0.00450 AC XY: 3271 AN XY: 727172

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.00161 AC: 72 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00169 AC: 146 AN: 86242

European-Finnish (FIN) AF: 0.00268 AC: 143 AN: 53384

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00548 AC: 6094 AN: 1111922

Other (OTH) AF: 0.00392 AC: 237 AN: 60396

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74474

African (AFR) AF: 0.000625 AC: 26 AN: 41568

American (AMR) AF: 0.00124 AC: 19 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00451 AC: 307 AN: 68018

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00291

EpiCase AF: 0.00387

EpiControl AF: 0.00356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		3.6
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147981592; hg19: chr9-100963778;