rs2243518

Variant names:

• chr8-94176622-T-A
• rs2243518
• NM_004063.4:c.343A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-94176622-T-A
• chr8-94176622-T-C
• chr8-94176622-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004063.4(CDH17):​c.343A>T​(p.Lys115*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH17 NM_004063.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 35 publications found

Genes affected

CDH17 (HGNC:1756): (cadherin 17) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ENSG00000304524 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004063.4. 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
	CDH17	NM_004063.4	MANE Select	c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	NP_004054.3
	CDH17	NM_001413951.1		c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	NP_001400880.1
	CDH17	NM_001144663.2		c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	NP_001138135.1	Q12864

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH17	ENST00000027335.8	TSL:1 MANE Select	c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	ENSP00000027335.3	Q12864
	CDH17	ENST00000450165.6	TSL:1	c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	ENSP00000401468.2	Q12864
	CDH17	ENST00000877574.1		c.343A>T	p.Lys115*	stop_gained	Exon 5 of 18	ENSP00000547633.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 110017

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.51	D
PhyloP100		0.13
Vest4		0.78
GERP RS		4.1
Mutation Taster		=19/181	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs2243518; hg19: chr8-95188850;