NM_016170.5:c.676C>A

Variant names:

• chr2-74516010-C-A
• rs1384198333
• NM_016170.5:c.676C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016170.5(TLX2):​c.676C>A​(p.Arg226Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000732 in 1,366,804 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R226G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TLX2 NM_016170.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80
• Publications: 0 publications found

Genes affected

TLX2 (HGNC:5057): (T cell leukemia homeobox 2) This gene is a member of an orphan homeobox-containing transcription factor family. Studies of the mouse ortholog have shown that the encoded protein is crucial for the development of the enteric nervous system; in humans, loss-of-function may play a role in tumorigenesis of gastrointestinal stromal tumors. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016170.5. 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
	TLX2	NM_016170.5	MANE Select	c.676C>A	p.Arg226Ser	missense	Exon 3 of 3	NP_057254.1	O43763

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLX2	ENST00000233638.8	TSL:1 MANE Select	c.676C>A	p.Arg226Ser	missense	Exon 3 of 3	ENSP00000233638.6	O43763
	TLX2	ENST00000621092.1	TSL:1	c.287C>A	p.Pro96Gln	missense	Exon 4 of 4	ENSP00000482690.1	F1T0F2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366804 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675120

African (AFR) AF: 0.00 AC: 0 AN: 28220

American (AMR) AF: 0.00 AC: 0 AN: 31992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22848

East Asian (EAS) AF: 0.00 AC: 0 AN: 33626

South Asian (SAS) AF: 0.00 AC: 0 AN: 75192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073952

Other (OTH) AF: 0.0000176 AC: 1 AN: 56734

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.077
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.62	D
PhyloP100		5.8
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.27
MVP		0.64
ClinPred		0.80	D
GERP RS		4.6
Varity_R		0.17
Mutation Taster		=88/12	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: rs1384198333; hg19: chr2-74743137;