chr5-19571762-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004934.5(CDH18):c.1070G>A(p.Arg357His) variant causes a missense change. The variant allele was found at a frequency of 0.0000936 in 1,613,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
CDH18
NM_004934.5 missense
NM_004934.5 missense
Scores
4
8
6
Clinical Significance
Conservation
PhyloP100: 5.81
Genes affected
CDH18 (HGNC:1757): (cadherin 18) This gene encodes a type II classical cadherin from the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH18 | NM_004934.5 | c.1070G>A | p.Arg357His | missense_variant | 8/13 | ENST00000382275.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH18 | ENST00000382275.6 | c.1070G>A | p.Arg357His | missense_variant | 8/13 | 1 | NM_004934.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000988 AC: 15AN: 151860Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250998Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135648
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GnomAD4 exome AF: 0.0000930 AC: 136AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 66AN XY: 727110
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GnomAD4 genome ? AF: 0.0000988 AC: 15AN: 151860Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7AN XY: 74136
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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 | Jun 18, 2021 | The c.1070G>A (p.R357H) alteration is located in exon 8 (coding exon 6) of the CDH18 gene. This alteration results from a G to A substitution at nucleotide position 1070, causing the arginine (R) at amino acid position 357 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;T;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L;.;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D;D;D;D
Sift4G
Uncertain
T;T;T;T;T;T;T
Polyphen
P;P;P;.;.;.;.
Vest4
MVP
MPC
0.62
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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