Variant 8-94152088-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004063.4(CDH17):c.1576G>C(p.Val526Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.02

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055843532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH17	NM_004063.4 linkuse as main transcript	c.1576G>C	p.Val526Leu	missense_variant	13/18	ENST00000027335.8
LOC105375647	XR_007061012.1 linkuse as main transcript	n.518+7815C>G		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.1576G>C	p.Val526Leu	missense_variant	13/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6 linkuse as main transcript	c.1576G>C	p.Val526Leu	missense_variant	13/18	1		P1
CDH17	ENST00000441892.6 linkuse as main transcript	c.934G>C	p.Val312Leu	missense_variant	9/13	2
CDH17	ENST00000520952.1 linkuse as main transcript	c.236-3214G>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152180

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

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

May 04, 2023

The c.1576G>C (p.V526L) alteration is located in exon 13 (coding exon 12) of the CDH17 gene. This alteration results from a G to C substitution at nucleotide position 1576, causing the valine (V) at amino acid position 526 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

Cadd

Benign

0.031

Dann

Benign

0.80

DEOGEN2

Benign

0.096

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.0054

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.019

B;B;B

Vest4

0.16

MutPred

0.46

Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);

MVP

0.36

MPC

0.069

ClinPred

0.065

GERP RS

-6.9

Varity_R

0.075

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over