13-27963117-A-G

Variant names:

• chr13-27963117-A-G
• rs1593181774
• NM_001265.6:c.940T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001265.6(CDX2):​c.940T>C​(p.Ter314Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDX2 NM_001265.6 stop_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.16
• 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]

ENSG00000310321 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001265.6 Downstream stopcodon found after 416 codons.
• PP5: Variant 13-27963117-A-G is Pathogenic according to our data. Variant chr13-27963117-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 812557.Status of the report is criteria_provided_single_submitter, 1 stars.

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.940T>C	p.Ter314Argext*?	stop_lost	Exon 3 of 3	NP_001256.4	Q99626
	CDX2	NM_001354700.2		c.*114T>C		3_prime_UTR	Exon 3 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.940T>C	p.Ter314Argext*?	stop_lost	Exon 3 of 3	ENSP00000370408.6	Q99626
	CDX2	ENST00000891171.1		c.964T>C	p.Ter322Argext*?	stop_lost	Exon 3 of 3	ENSP00000561230.1
	CDX2	ENST00000947371.1		c.940T>C	p.Ter314Argext*?	stop_lost	Exon 4 of 4	ENSP00000617430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Sirenomelia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=57/143	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1593181774; hg19: chr13-28537254;