Variant 9-105662716-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005421.3(TAL2):c.220A>G(p.Ile74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 1,454,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TAL2
NM_005421.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.352

Variant links:

Genes affected

TAL2 (HGNC:11557): (TAL bHLH transcription factor 2) This intronless gene encodes a helix-loop-helix protein. Translocations between this gene on chromosome 9 and the T-cell receptor beta-chain locus on chromosome 7 have been associated with activation of the T-cell acute lymphocytic leukemia 2 gene and T-cell acute lymphoblastic leukemia. [provided by RefSeq, Mar 2009]

TAL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045929074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAL2	NM_005421.3 linkuse as main transcript	c.220A>G	p.Ile74Val	missense_variant	1/1	ENST00000334077.6	NP_005412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAL2	ENST00000334077.6 linkuse as main transcript	c.220A>G	p.Ile74Val	missense_variant	1/1		NM_005421.3	ENSP00000334547	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

245110

Hom.:

AF XY:

0.0000226

AC XY:

AN XY:

132458

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1454882

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723156

show subpopulations

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.220A>G (p.I74V) alteration is located in exon 1 (coding exon 1) of the TAL2 gene. This alteration results from a A to G substitution at nucleotide position 220, causing the isoleucine (I) at amino acid position 74 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.24

CADD

Benign

5.2

DANN

Benign

0.49

DEOGEN2

Benign

0.052

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.58

M_CAP

Benign

0.038

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.93

PrimateAI

Benign

0.43

PROVEAN

Benign

0.30

REVEL

Benign

0.22

Sift

Benign

0.63

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.13

MutPred

0.43

Gain of relative solvent accessibility (P = 0.1571);

MVP

0.63

MPC

0.025

ClinPred

0.038

GERP RS

-3.5

Varity_R

0.030

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over