13-27968673-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001265.6(CDX2):​c.334G>A​(p.Asp112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,533,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D112A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CDX2
NM_001265.6 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.36518556).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDX2NM_001265.6 linkc.334G>A p.Asp112Asn missense_variant Exon 1 of 3 ENST00000381020.8 NP_001256.4 Q99626
CDX2NM_001354700.2 linkc.334G>A p.Asp112Asn missense_variant Exon 1 of 3 NP_001341629.1
CDX2XM_011534875.3 linkc.334G>A p.Asp112Asn missense_variant Exon 1 of 3 XP_011533177.1
CDX2XM_011534876.3 linkc.334G>A p.Asp112Asn missense_variant Exon 1 of 3 XP_011533178.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDX2ENST00000381020.8 linkc.334G>A p.Asp112Asn missense_variant Exon 1 of 3 1 NM_001265.6 ENSP00000370408.6 Q99626

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.24e-7
AC:
1
AN:
1381396
Hom.:
0
Cov.:
31
AF XY:
0.00000147
AC XY:
1
AN XY:
681844
show subpopulations
Gnomad4 AFR exome
AF:
0.0000331
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.334G>A (p.D112N) alteration is located in exon 1 (coding exon 1) of the CDX2 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the aspartic acid (D) at amino acid position 112 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.77
T
M_CAP
Pathogenic
0.34
D
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.094
Sift
Benign
0.098
T
Sift4G
Benign
0.088
T
Polyphen
0.66
P
Vest4
0.18
MutPred
0.58
Gain of catalytic residue at Y107 (P = 0.0011);
MVP
0.77
MPC
0.72
ClinPred
0.78
D
GERP RS
3.6
Varity_R
0.13
gMVP
0.67

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.

Other links and lift over

dbSNP: rs1345464021; hg19: chr13-28542810; API