dbSNP rs779324842: CDX2:p.Arg163Leu (chr13-27968519-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_001265.6(CDX2):c.488G>T(p.Arg163Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000354 in 1,412,128 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. R163Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CDX2
NM_001265.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17

Variant links:

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]

CDX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDX2	NM_001265.6 link	c.488G>T	p.Arg163Leu	missense_variant	Exon 1 of 3	ENST00000381020.8	NP_001256.4	Q99626

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDX2	ENST00000381020.8 link	c.488G>T	p.Arg163Leu	missense_variant	Exon 1 of 3	1	NM_001265.6	ENSP00000370408.6		Q99626

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000354

AC:

AN:

1412128

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

702658

show subpopulations

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:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.19

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.73

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Benign

0.062

Polyphen

0.75

Vest4

0.33

MutPred

0.56

Gain of catalytic residue at Q161 (P = 0.0042);

MVP

0.67

MPC

1.8

ClinPred

0.98

GERP RS

4.0

Varity_R

0.44

gMVP

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over