NM_003260.5:c.2212G>A

Variant names:

• chr19-2997868-C-T
• rs200647783
• NM_003260.5:c.2212G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003260.5(TLE2):​c.2212G>A​(p.Val738Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000621 in 1,610,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: TLE2 NM_003260.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93
• Publications: 2 publications found

Genes affected

TLE2 (HGNC:11838): (TLE family member 2, transcriptional corepressor) Enables transcription corepressor activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription, DNA-templated. Located in focal adhesion and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.39245728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003260.5. 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
	TLE2	NM_003260.5	MANE Select	c.2212G>A	p.Val738Met	missense	Exon 20 of 20	NP_003251.2
	TLE2	NM_001300846.2		c.2215G>A	p.Val739Met	missense	Exon 20 of 20	NP_001287775.1	K7EMK7
	TLE2	NM_001144762.2		c.1846G>A	p.Val616Met	missense	Exon 18 of 18	NP_001138234.1	Q04725-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE2	ENST00000262953.11	TSL:1 MANE Select	c.2212G>A	p.Val738Met	missense	Exon 20 of 20	ENSP00000262953.5	Q04725-1
	TLE2	ENST00000590536.5	TSL:1	c.2215G>A	p.Val739Met	missense	Exon 20 of 20	ENSP00000466542.1	K7EMK7
	TLE2	ENST00000591529.5	TSL:1	c.*56G>A		3_prime_UTR	Exon 20 of 20	ENSP00000468279.1	Q04725-3

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152008 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000697 AC: 17 AN: 243928 AF XY: 0.0000529

Gnomad AFR exome AF: 0.000875

Gnomad AMR exome AF: 0.0000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000439 AC: 64 AN: 1458062 Hom.: 0 Cov.: 30 AF XY: 0.0000428 AC XY: 31 AN XY: 724944

African (AFR) AF: 0.00141 AC: 47 AN: 33428

American (AMR) AF: 0.000113 AC: 5 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110152

Other (OTH) AF: 0.0000995 AC: 6 AN: 60274

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152126 Hom.: 0 Cov.: 31 AF XY: 0.000242 AC XY: 18 AN XY: 74368

African (AFR) AF: 0.000771 AC: 32 AN: 41490

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.000123 Hom.: 0

Bravo AF: 0.000385

ESP6500AA AF: 0.00122 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000116 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.022	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.79
MVP		0.85
MPC		1.6
ClinPred		0.18	T
GERP RS		4.2
Varity_R		0.14
gMVP		0.68
Mutation Taster		=87/13	polymorphism

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: rs200647783; hg19: chr19-2997866;