18-65822106-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004361.5(CDH7):ā€‹c.651C>Gā€‹(p.Asn217Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CDH7
NM_004361.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3179731).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH7NM_004361.5 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/12 ENST00000397968.4
CDH7NM_001362438.2 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/12
CDH7NM_033646.4 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/12
CDH7NM_001317214.3 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH7ENST00000397968.4 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/121 NM_004361.5 P1
CDH7ENST00000323011.7 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/121 P1
CDH7ENST00000536984.6 linkuse as main transcriptc.651C>G p.Asn217Lys missense_variant 5/111

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251232
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460836
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726788
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 31, 2024The c.651C>G (p.N217K) alteration is located in exon 5 (coding exon 4) of the CDH7 gene. This alteration results from a C to G substitution at nucleotide position 651, causing the asparagine (N) at amino acid position 217 to be replaced by a lysine (K). 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
Uncertain
0.48
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.87
.;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.030
N;.;N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-4.3
D;D;D
REVEL
Benign
0.21
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.13
T;T;T
Polyphen
0.61
P;D;P
Vest4
0.46
MutPred
0.56
Gain of glycosylation at N217 (P = 0.0269);Gain of glycosylation at N217 (P = 0.0269);Gain of glycosylation at N217 (P = 0.0269);
MVP
0.61
MPC
1.0
ClinPred
0.87
D
GERP RS
5.0
Varity_R
0.36
gMVP
0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1272393362; hg19: chr18-63489342; API