rs121434539
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The NM_004933.3(CDH15):c.178C>T(p.Arg60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,606,632 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
CDH15
NM_004933.3 missense
NM_004933.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 0.671
Genes affected
CDH15 (HGNC:1754): (cadherin 15) This gene is a member of the cadherin superfamily of genes, encoding calcium-dependent intercellular adhesion glycoproteins. Cadherins consist of an extracellular domain containing 5 cadherin domains, a transmembrane region, and a conserved cytoplasmic domain. Transcripts from this particular cadherin are expressed in myoblasts and upregulated in myotubule-forming cells. The protein is thought to be essential for the control of morphogenetic processes, specifically myogenesis, and may provide a trigger for terminal muscle cell differentiation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.33291668).
BP6
Variant 16-89179551-C-T is Benign according to our data. Variant chr16-89179551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 17642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH15 | NM_004933.3 | c.178C>T | p.Arg60Cys | missense_variant | 2/14 | ENST00000289746.3 | NP_004924.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH15 | ENST00000289746.3 | c.178C>T | p.Arg60Cys | missense_variant | 2/14 | 1 | NM_004933.3 | ENSP00000289746.2 | ||
CDH15 | ENST00000521087.5 | n.243C>T | non_coding_transcript_exon_variant | 2/3 | 5 | |||||
CDH15 | ENST00000524089.1 | n.243C>T | non_coding_transcript_exon_variant | 2/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000118 AC: 29AN: 245476Hom.: 0 AF XY: 0.000143 AC XY: 19AN XY: 132780
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GnomAD4 exome AF: 0.0000509 AC: 74AN: 1454434Hom.: 0 Cov.: 32 AF XY: 0.0000609 AC XY: 44AN XY: 722864
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74350
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 3 Pathogenic:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 19, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2008 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 18, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
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