rs372415979

Variant names:

• chr2-74514813-C-A
• NM_016170.5:c.7C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-74514813-C-A
• chr2-74514813-C-T

Variant summary

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

The NM_016170.5(TLX2):​c.7C>A​(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TLX2 NM_016170.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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

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=0.35478175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLX2	NM_016170.5	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 3	ENST00000233638.8	NP_057254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLX2	ENST00000233638.8	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 3	1	NM_016170.5	ENSP00000233638.6
TLX2	ENST00000621092.1	c.11+579C>A		intron_variant	Intron 2 of 3	1		ENSP00000482690.1
TLX2	ENST00000497238.1	n.522-209C>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460346 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726552

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.037	D
Polyphen		0.60	P
Vest4		0.29
MutPred		0.34		Gain of phosphorylation at P3 (P = 0.0554);
MVP		0.80
MPC		1.1
ClinPred		0.37	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.77

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: chr2-74741940;