18-65822106-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004361.5(CDH7):āc.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
NM_004361.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 1.42
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]
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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 |
---|---|---|---|---|---|---|---|
CDH7 | NM_004361.5 | c.651C>G | p.Asn217Lys | missense_variant | 5/12 | ENST00000397968.4 | |
CDH7 | NM_001362438.2 | c.651C>G | p.Asn217Lys | missense_variant | 5/12 | ||
CDH7 | NM_033646.4 | c.651C>G | p.Asn217Lys | missense_variant | 5/12 | ||
CDH7 | NM_001317214.3 | c.651C>G | p.Asn217Lys | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH7 | ENST00000397968.4 | c.651C>G | p.Asn217Lys | missense_variant | 5/12 | 1 | NM_004361.5 | P1 | |
CDH7 | ENST00000323011.7 | c.651C>G | p.Asn217Lys | missense_variant | 5/12 | 1 | P1 | ||
CDH7 | ENST00000536984.6 | c.651C>G | p.Asn217Lys | missense_variant | 5/11 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251232Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135802
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460836Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726788
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GnomAD4 genome Cov.: 32
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 submitter | clinical testing | Ambry Genetics | Mar 31, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;D;P
Vest4
MutPred
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
MPC
1.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at