rs17715450
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001793.6(CDH3):c.2239C>A(p.Arg747=) variant causes a synonymous change. The variant allele was found at a frequency of 0.566 in 1,613,546 control chromosomes in the GnomAD database, including 262,681 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.50 ( 20056 hom., cov: 31)
Exomes 𝑓: 0.57 ( 242625 hom. )
Consequence
CDH3
NM_001793.6 synonymous
NM_001793.6 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 5.74
Genes affected
CDH3 (HGNC:1762): (cadherin 3) This gene encodes a 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 protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 16-68695882-C-A is Benign according to our data. Variant chr16-68695882-C-A is described in ClinVar as [Benign]. Clinvar id is 93783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-68695882-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH3 | NM_001793.6 | c.2239C>A | p.Arg747= | synonymous_variant | 15/16 | ENST00000264012.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH3 | ENST00000264012.9 | c.2239C>A | p.Arg747= | synonymous_variant | 15/16 | 1 | NM_001793.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.499 AC: 75739AN: 151838Hom.: 20056 Cov.: 31
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GnomAD3 exomes AF: 0.533 AC: 133886AN: 251290Hom.: 36494 AF XY: 0.541 AC XY: 73533AN XY: 135852
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GnomAD4 exome AF: 0.573 AC: 837586AN: 1461590Hom.: 242625 Cov.: 51 AF XY: 0.573 AC XY: 416511AN XY: 727110
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GnomAD4 genome ? AF: 0.499 AC: 75758AN: 151956Hom.: 20056 Cov.: 31 AF XY: 0.498 AC XY: 36953AN XY: 74250
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
EEM syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 02, 2013 | - - |
Congenital hypotrichosis with juvenile macular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
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