rs199863291

Variant names:

• chr19-2997944-C-A
• ENST00000591529.5:c.2101G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-2997944-C-A
• chr19-2997944-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144761.2(TLE2):​c.2101G>T​(p.Val701Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TLE2 NM_001144761.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.22

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29684478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE2	NM_003260.5	c.2136G>T	p.Ser712Ser	synonymous_variant	Exon 20 of 20	ENST00000262953.11	NP_003251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE2	ENST00000262953.11	c.2136G>T	p.Ser712Ser	synonymous_variant	Exon 20 of 20	1	NM_003260.5	ENSP00000262953.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459538 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725868

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.0040
DANN	Benign	0.70
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.36	T;.
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.19	T
PROVEAN	Benign	-0.48	N;.
REVEL	Benign	0.27
Sift	Benign	0.032	D;.
Sift4G	Benign	0.18	T;T
Vest4		0.24
MutPred		0.80		Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);
MVP		0.21
ClinPred		0.15	T
GERP RS		-8.4

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: chr19-2997942;