Genetic Variant CDH17:p.Glu739Gly (chr8-94130944-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004063.4(CDH17):c.2216A>G(p.Glu739Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E739A) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369

Publications

42 publications found

Variant links:

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 links:

ENSG00000304524 (HGNC:):

ENSG00000304524 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15899205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH17	NM_004063.4 link	c.2216A>G	p.Glu739Gly	missense_variant	Exon 16 of 18	ENST00000027335.8	NP_004054.3	Q12864

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8 link	c.2216A>G	p.Glu739Gly	missense_variant	Exon 16 of 18	1	NM_004063.4	ENSP00000027335.3		Q12864

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1457366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725378

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107956

Other (OTH)

AF:

0.00

AC:

AN:

60260

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

92325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.31

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L

PhyloP100

0.37

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.014

B;P;B

Vest4

0.15

MutPred

0.35

Loss of stability (P = 0.0075);.;Loss of stability (P = 0.0075);

MVP

0.38

MPC

0.080

ClinPred

0.30

GERP RS

0.45

Varity_R

0.049

gMVP

0.72

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over