rs2243518

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

CDH17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH17	NM_004063.4	c.343A>T	p.Lys115*	stop_gained	5/18	ENST00000027335.8	NP_004054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8	c.343A>T	p.Lys115*	stop_gained	5/18	1	NM_004063.4	ENSP00000027335.3
CDH17	ENST00000450165.6	c.343A>T	p.Lys115*	stop_gained	5/18	1		ENSP00000401468.2
CDH17	ENST00000441892.6	c.343A>T	p.Lys115*	stop_gained	5/13	2		ENSP00000392811.2
CDH17	ENST00000521491.1	c.343A>T	p.Lys115*	stop_gained	6/7	5		ENSP00000428189.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
Vest4		0.78
GERP RS		4.1

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

Other links and lift over

dbSNP: rs2243518; hg19: chr8-95188850;