8-94148752-G-C

Variant summary

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

The NM_004063.4(CDH17):c.1919C>G(p.Thr640Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 992,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

CDH17
NM_004063.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26177546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH17	NM_004063.4 linkuse as main transcript	c.1919C>G	p.Thr640Arg	missense_variant	14/18	ENST00000027335.8
LOC105375647	XR_007061012.1 linkuse as main transcript	n.518+4479G>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.1919C>G	p.Thr640Arg	missense_variant	14/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6 linkuse as main transcript	c.1919C>G	p.Thr640Arg	missense_variant	14/18	1		P1
CDH17	ENST00000441892.6 linkuse as main transcript	c.1277C>G	p.Thr426Arg	missense_variant	10/13	2
CDH17	ENST00000520952.1 linkuse as main transcript	c.*87C>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

97022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000427

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:

0.000193

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

158580

Hom.:

AF XY:

0.0000458

AC XY:

AN XY:

87368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

243

AN:

895180

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

119

AN XY:

445744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000338

Gnomad4 OTH exome

AF:

0.000145

GnomAD4 genome

AF:

0.000113

AC:

AN:

97022

Hom.:

Cov.:

AF XY:

0.0000895

AC XY:

AN XY:

44672

show subpopulations

Gnomad4 AFR

AF:

0.0000427

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:

0.000193

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000988

Hom.:

ExAC

AF:

0.0000577

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

Jan 26, 2023

The c.1919C>G (p.T640R) alteration is located in exon 14 (coding exon 13) of the CDH17 gene. This alteration results from a C to G substitution at nucleotide position 1919, causing the threonine (T) at amino acid position 640 to be replaced by an arginine (R). 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

0.072

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.20

T;.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.65

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

L;.;L

MutationTaster

Benign

0.78

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;D;N

REVEL

Benign

0.23

Sift

Benign

0.28

T;T;T

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.82

P;B;P

Vest4

0.47

MVP

0.80

MPC

0.084

ClinPred

0.14

GERP RS

4.6

Varity_R

0.25

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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