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. Variant has been reported in ClinVar as (no stars). 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).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH17	NM_004063.4	MANE Select	c.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	NP_004054.3
CDH17	NM_001413951.1		c.2273A>G	p.Glu758Gly	missense	Exon 16 of 18	NP_001400880.1
CDH17	NM_001144663.2		c.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	NP_001138135.1	Q12864

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH17	ENST00000027335.8	TSL:1 MANE Select	c.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	ENSP00000027335.3	Q12864
CDH17	ENST00000450165.6	TSL:1	c.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	ENSP00000401468.2	Q12864
CDH17	ENST00000877574.1		c.2273A>G	p.Glu758Gly	missense	Exon 16 of 18	ENSP00000547633.1

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 v4.9

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.59

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.37

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

REVEL

Benign

0.025

Sift

Benign

0.23

Sift4G

Benign

0.17

Polyphen

0.014

Vest4

0.15

MutPred

0.35

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over