chr16-64950780-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001797.4(CDH11):c.1881C>G(p.Ile627Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CDH11
NM_001797.4 missense
NM_001797.4 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 0.405
Genes affected
CDH11 (HGNC:1750): (cadherin 11) This gene encodes a type II classical cadherin from the cadherin superfamily, 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. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH11 | NM_001797.4 | c.1881C>G | p.Ile627Met | missense_variant | 12/13 | ENST00000268603.9 | |
CDH11 | NM_001308392.2 | c.1881C>G | p.Ile627Met | missense_variant | 12/14 | ||
CDH11 | NM_001330576.2 | c.1503C>G | p.Ile501Met | missense_variant | 11/12 | ||
CDH11 | XM_047433486.1 | c.1503C>G | p.Ile501Met | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH11 | ENST00000268603.9 | c.1881C>G | p.Ile627Met | missense_variant | 12/13 | 1 | NM_001797.4 | P1 | |
CDH11 | ENST00000394156.7 | c.1881C>G | p.Ile627Met | missense_variant | 12/14 | 1 | |||
CDH11 | ENST00000566827.5 | c.1503C>G | p.Ile501Met | missense_variant | 11/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461396Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726890
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2024 | The c.1881C>G (p.I627M) alteration is located in exon 12 (coding exon 10) of the CDH11 gene. This alteration results from a C to G substitution at nucleotide position 1881, causing the isoleucine (I) at amino acid position 627 to be replaced by a methionine (M). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;D;D
Sift4G
Uncertain
D;T;D
Polyphen
D;P;.
Vest4
MutPred
Loss of stability (P = 0.3615);Loss of stability (P = 0.3615);.;
MVP
MPC
0.75
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