13-27968528-C-T

Variant names:

• chr13-27968528-C-T
• NM_001265.6:c.479G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001265.6(CDX2):​c.479G>A​(p.Gly160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: CDX2 NM_001265.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.905

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21213979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDX2	NM_001265.6	c.479G>A	p.Gly160Asp	missense_variant	Exon 1 of 3	ENST00000381020.8	NP_001256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDX2	ENST00000381020.8	c.479G>A	p.Gly160Asp	missense_variant	Exon 1 of 3	1	NM_001265.6	ENSP00000370408.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1412108 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 702630

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.479G>A (p.G160D) 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 479, causing the glycine (G) at amino acid position 160 to be replaced by an aspartic acid (D). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.21	T
Sift4G	Benign	0.65	T
Polyphen		0.39	B
Vest4		0.14
MutPred		0.45		Gain of catalytic residue at Q161 (P = 0.0086);
MVP		0.40
MPC		1.4
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.42
gMVP		0.79

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: chr13-28542665;