8-94148852-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004063.4(CDH17):c.1819A>G(p.Arg607Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,611,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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:

LOC105375647 (HGNC:):

LOC105375647 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
CDH17	NM_004063.4 linkuse as main transcript	c.1819A>G	p.Arg607Gly	missense_variant	14/18	ENST00000027335.8
LOC105375647	XR_007061012.1 linkuse as main transcript	n.518+4579T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDH17	ENST00000027335.8 linkuse as main transcript	c.1819A>G	p.Arg607Gly	missense_variant	14/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6 linkuse as main transcript	c.1819A>G	p.Arg607Gly	missense_variant	14/18	1		P1
CDH17	ENST00000441892.6 linkuse as main transcript	c.1177A>G	p.Arg393Gly	missense_variant	10/13	2
CDH17	ENST00000520952.1 linkuse as main transcript	c.260A>G	p.Lys87Arg	missense_variant, NMD_transcript_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000926

AC:

AN:

248308

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

134242

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1459280

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

725946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151914

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.000120

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.1819A>G (p.R607G) alteration is located in exon 14 (coding exon 13) of the CDH17 gene. This alteration results from a A to G substitution at nucleotide position 1819, causing the arginine (R) at amino acid position 607 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.;T

Eigen

Benign

0.027

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.23

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.57

MVP

0.79

MPC

0.22

ClinPred

0.15

GERP RS

3.4

Varity_R

0.29

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over