Genetic Variant NM_004062.4:c.2296G>A (chr16-66909363-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004062.4(CDH16):c.2296G>A(p.Val766Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,397,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CDH16
NM_004062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.391

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.112303734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH16	NM_004062.4	MANE Select	c.2296G>A	p.Val766Met	missense	Exon 17 of 18	NP_004053.1	O75309-1
CDH16	NM_001204744.2		c.2230G>A	p.Val744Met	missense	Exon 17 of 18	NP_001191673.1	O75309-2
CDH16	NM_001204745.2		c.2179G>A	p.Val727Met	missense	Exon 17 of 18	NP_001191674.1	O75309-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH16	ENST00000299752.9	TSL:1 MANE Select	c.2296G>A	p.Val766Met	missense	Exon 17 of 18	ENSP00000299752.4	O75309-1
CDH16	ENST00000394055.7	TSL:1	c.2230G>A	p.Val744Met	missense	Exon 17 of 18	ENSP00000377619.3	O75309-2
CDH16	ENST00000568632.5	TSL:1	c.2005G>A	p.Val669Met	missense	Exon 16 of 17	ENSP00000455263.1	O75309-3

Frequencies

GnomAD3 genomes

AF:

0.0000346

AC:

AN:

144652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000233

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000321

AC:

AN:

249484

AF XY:

0.0000518

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1252710

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

621766

show subpopulations

African (AFR)

AF:

0.0000366

AC:

AN:

27348

American (AMR)

AF:

0.0000521

AC:

AN:

38400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18310

East Asian (EAS)

AF:

0.00

AC:

AN:

20186

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.0000255

AC:

AN:

978942

Other (OTH)

AF:

0.0000215

AC:

AN:

46404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000346

AC:

AN:

144652

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

70434

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40242

American (AMR)

AF:

0.000137

AC:

AN:

14638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3352

East Asian (EAS)

AF:

0.000233

AC:

AN:

4296

South Asian (SAS)

AF:

0.00

AC:

AN:

4084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65562

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.66

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.39

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.88

REVEL

Benign

0.043

Sift

Benign

0.073

Sift4G

Benign

0.11

Polyphen

0.0080

Vest4

0.32

MVP

0.44

MPC

0.069

ClinPred

0.11

GERP RS

0.81

Varity_R

0.040

gMVP

0.27

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over