Genetic Variant CDH16:p.Val766Leu (chr16-66909363-C-A) – 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>T(p.Val766Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,252,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V766M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

CDH16
NM_004062.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

Publications

0 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:

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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=0.13558456).

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>T	p.Val766Leu	missense	Exon 17 of 18	NP_004053.1	O75309-1
CDH16	NM_001204744.2		c.2230G>T	p.Val744Leu	missense	Exon 17 of 18	NP_001191673.1	O75309-2
CDH16	NM_001204745.2		c.2179G>T	p.Val727Leu	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>T	p.Val766Leu	missense	Exon 17 of 18	ENSP00000299752.4	O75309-1
CDH16	ENST00000394055.7	TSL:1	c.2230G>T	p.Val744Leu	missense	Exon 17 of 18	ENSP00000377619.3	O75309-2
CDH16	ENST00000568632.5	TSL:1	c.2005G>T	p.Val669Leu	missense	Exon 16 of 17	ENSP00000455263.1	O75309-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.98e-7

AC:

AN:

1252710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27348

American (AMR)

AF:

0.00

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:

0.00

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:

0.00000102

AC:

AN:

978942

Other (OTH)

AF:

0.00

AC:

AN:

46404

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.67

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.39

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.071

Sift

Benign

0.051

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.26

MutPred

0.59

Loss of catalytic residue at V766 (P = 0.0469)

MVP

0.43

MPC

0.067

ClinPred

0.33

GERP RS

0.81

Varity_R

0.070

gMVP

0.28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over