chr2-74516031-C-T

Variant names:

• chr2-74516031-C-T
• NM_016170.5:c.697C>T

Variant summary

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

The NM_016170.5(TLX2):​c.697C>T​(p.His233Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLX2 NM_016170.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• 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.697C>T	p.His233Tyr	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.697C>T	p.His233Tyr	missense	Exon 3 of 3	ENSP00000233638.6	O43763
	TLX2	ENST00000621092.1	TSL:1	c.308C>T	p.Ala103Val	missense	Exon 4 of 4	ENSP00000482690.1	F1T0F2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1404818 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 696518

African (AFR) AF: 0.00 AC: 0 AN: 29414

American (AMR) AF: 0.00 AC: 0 AN: 38180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24788

East Asian (EAS) AF: 0.00 AC: 0 AN: 35166

South Asian (SAS) AF: 0.00 AC: 0 AN: 80766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091066

Other (OTH) AF: 0.00 AC: 0 AN: 58318

GnomAD4 genome Cov.: 33

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	0.20
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.62	D
PhyloP100		6.1
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.68
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.13
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-74743158;