13-27963122-G-C

Variant names:

• chr13-27963122-G-C
• NM_001265.6:c.935C>G

Variant summary

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

The NM_001265.6(CDX2):​c.935C>G​(p.Thr312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDX2 NM_001265.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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=0.19122887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDX2	NM_001265.6	c.935C>G	p.Thr312Ser	missense_variant	Exon 3 of 3	ENST00000381020.8	NP_001256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDX2	ENST00000381020.8	c.935C>G	p.Thr312Ser	missense_variant	Exon 3 of 3	1	NM_001265.6	ENSP00000370408.6
CDX2	ENST00000548877.1	n.463C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459392 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 725574

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.935C>G (p.T312S) alteration is located in exon 3 (coding exon 3) of the CDX2 gene. This alteration results from a C to G substitution at nucleotide position 935, causing the threonine (T) at amino acid position 312 to be replaced by a serine (S). 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	Benign	0.11
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.086
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.033	B
Vest4		0.089
MutPred		0.13		Loss of glycosylation at T312 (P = 0.0372);
MVP		0.74
MPC		0.61
ClinPred		0.44	T
GERP RS		5.4
Varity_R		0.31
gMVP		0.46

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: chr13-28537259;