13-27968589-G-A

Variant names:

• chr13-27968589-G-A
• rs1361731354
• NM_001265.6:c.418C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001265.6(CDX2):​c.418C>T​(p.Leu140Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L140V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDX2 NM_001265.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

Genes affected

CDX2 (HGNC:1806): (caudal type homeobox 2) This gene is a member of the caudal-related homeobox transcription factor gene family. The encoded protein is a major regulator of intestine-specific genes involved in cell growth an differentiation. This protein also plays a role in early embryonic development of the intestinal tract. Aberrant expression of this gene is associated with intestinal inflammation and tumorigenesis. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.0581 (below the threshold of 3.09). Trascript score misZ: -0.02091 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265.6. 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
	CDX2	NM_001265.6	MANE Select	c.418C>T	p.Leu140Phe	missense	Exon 1 of 3	NP_001256.4	Q99626
	CDX2	NM_001354700.2		c.418C>T	p.Leu140Phe	missense	Exon 1 of 3	NP_001341629.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDX2	ENST00000381020.8	TSL:1 MANE Select	c.418C>T	p.Leu140Phe	missense	Exon 1 of 3	ENSP00000370408.6	Q99626
	CDX2	ENST00000891171.1		c.418C>T	p.Leu140Phe	missense	Exon 1 of 3	ENSP00000561230.1
	CDX2	ENST00000947371.1		c.418C>T	p.Leu140Phe	missense	Exon 2 of 4	ENSP00000617430.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.0082
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.086	D
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.36
Sift	Benign	0.27	T
Sift4G	Benign	0.082	T
Polyphen		0.98	D
Vest4		0.16
MutPred		0.58		Gain of catalytic residue at P144 (P = 5e-04)
MVP		0.85
MPC		1.2
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.19
gMVP		0.73
Mutation Taster		=87/13	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: rs1361731354; hg19: chr13-28542726; COSMIC: COSV101122657; COSMIC: COSV101122657;