NM_005421.3:c.282G>C

Variant names:

• chr9-105662778-G-C
• NM_005421.3:c.282G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005421.3(TAL2):​c.282G>C​(p.Glu94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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)
• Consequence: TAL2 NM_005421.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.254
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036865145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005421.3. 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
	TAL2	NM_005421.3	MANE Select	c.282G>C	p.Glu94Asp	missense	Exon 1 of 1	NP_005412.1	Q16559

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL2	ENST00000334077.6	TSL:6 MANE Select	c.282G>C	p.Glu94Asp	missense	Exon 1 of 1	ENSP00000334547.3	Q16559

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.070
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.9
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.25
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.12
Sift	Benign	0.93	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.23		Loss of disorder (P = 0.1822)
MVP		0.68
MPC		0.026
ClinPred		0.024	T
GERP RS		0.37
PromoterAI		0.0029	Neutral
Varity_R		0.051
gMVP		0.25
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr9-108425059;