Genetic Variant NM_004361.5:c.16G>A (chr18-65762858-G-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_004361.5(CDH7):c.16G>A(p.Val6Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. V6L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDH7
NM_004361.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.67

Publications

0 publications found

Variant links:

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

CDH7 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=0.17766869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2	Q9ULB5
CDH7	NM_001362438.2 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 12		NP_387450.1	Q9ULB5
CDH7	NM_001317214.3 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 11		NP_001304143.1	Q9ULB5F5H5X9Q8IY78

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDH7	ENST00000397968.4 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2	Q9ULB5
CDH7	ENST00000323011.7 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 12	1		ENSP00000319166.3	Q9ULB5
CDH7	ENST00000536984.6 link	c.16G>A	p.Val6Met	missense_variant	Exon 2 of 11	1		ENSP00000443030.2	F5H5X9
CDH7	ENST00000581601.1 link	n.-150G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.00

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111068

Other (OTH)

AF:

0.00

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

.;D;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.69

N;.;N

PhyloP100

5.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.52

N;N;N

REVEL

Benign

0.099

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.83

P;B;P

Vest4

0.41

MutPred

0.36

Loss of methylation at K5 (P = 0.0137);Loss of methylation at K5 (P = 0.0137);Loss of methylation at K5 (P = 0.0137);

MVP

0.46

MPC

0.35

ClinPred

0.51

GERP RS

5.8

Varity_R

0.10

gMVP

0.65

Mutation Taster

=88/12

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

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NM_004361.5:c.16G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over