8-94145999-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004063.4(CDH17):c.2096G>A(p.Arg699Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R699W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.169

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20590204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH17	NM_004063.4 linkuse as main transcript	c.2096G>A	p.Arg699Gln	missense_variant	15/18	ENST00000027335.8
LOC105375647	XR_007061012.1 linkuse as main transcript	n.518+1726C>T		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.2096G>A	p.Arg699Gln	missense_variant	15/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6 linkuse as main transcript	c.2096G>A	p.Arg699Gln	missense_variant	15/18	1		P1
CDH17	ENST00000441892.6 linkuse as main transcript	c.1454G>A	p.Arg485Gln	missense_variant	11/13	2
CDH17	ENST00000520952.1 linkuse as main transcript	c.*264G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250638

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

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

Sep 12, 2023

The c.2096G>A (p.R699Q) alteration is located in exon 15 (coding exon 14) of the CDH17 gene. This alteration results from a G to A substitution at nucleotide position 2096, causing the arginine (R) at amino acid position 699 to be replaced by a glutamine (Q). 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

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.035

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.29

MutPred

0.51

Loss of catalytic residue at R699 (P = 0.1009);.;Loss of catalytic residue at R699 (P = 0.1009);

MVP

0.71

MPC

0.12

ClinPred

0.31

GERP RS

3.0

Varity_R

0.053

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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