16-66910277-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004062.4(CDH16):c.2150G>A(p.Arg717His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,604,458 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R717C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.025 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 146 hom. )

Consequence

CDH16
NM_004062.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.164

Variant links:

Genes affected

CDH16 (HGNC:1755): (cadherin 16) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. Mapped to a previously identified cluster of cadherin genes on chromosome 16q22.1, the gene localizes with superfamily members CDH1, CDH3, CDH5, CDH8 and CDH11. The protein consists of an extracellular domain containing 6 cadherin domains, a transmembrane region and a truncated cytoplasmic domain but lacks the prosequence and tripeptide HAV adhesion recognition sequence typical of most classical cadherins. Expression is exclusively in kidney, where the protein functions as the principal mediator of homotypic cellular recognition, playing a role in the morphogenic direction of tissue development. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

CDH16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004127145).

BP6

Variant 16-66910277-C-T is Benign according to our data. Variant chr16-66910277-C-T is described in ClinVar as [Benign]. Clinvar id is 784344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH16	NM_004062.4 link	c.2150G>A	p.Arg717His	missense_variant	Exon 15 of 18	ENST00000299752.9	NP_004053.1	O75309-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH16	ENST00000299752.9 link	c.2150G>A	p.Arg717His	missense_variant	Exon 15 of 18	1	NM_004062.4	ENSP00000299752.4		O75309-1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3795

AN:

152134

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00688

AC:

1673

AN:

243124

Hom.:

AF XY:

0.00471

AC XY:

617

AN XY:

131088

show subpopulations

Gnomad AFR exome

AF:

0.0922

Gnomad AMR exome

AF:

0.00418

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000207

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

AF:

0.00245

AC:

3562

AN:

1452206

Hom.:

146

Cov.:

AF XY:

0.00213

AC XY:

1536

AN XY:

721468

show subpopulations

Gnomad4 AFR exome

AF:

0.0881

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000213

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000876

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.0249

AC:

3795

AN:

152252

Hom.:

165

Cov.:

AF XY:

0.0242

AC XY:

1799

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0875

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00483

Hom.:

Bravo

AF:

0.0291

ESP6500AA

AF:

0.0848

AC:

373

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00816

AC:

990

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

.;T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.88

D;D;D;D;D

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;M;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.63

P;B;.;.;.

Vest4

0.16

MVP

0.58

MPC

0.10

ClinPred

0.026

GERP RS

3.9

Varity_R

0.058

gMVP

0.36

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