chr20-46178098-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021248.3(CDH22):c.1763C>T(p.Thr588Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,974 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 1 hom. )
Consequence
CDH22
NM_021248.3 missense
NM_021248.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.98
Genes affected
CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10939863).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH22 | NM_021248.3 | c.1763C>T | p.Thr588Ile | missense_variant | 11/12 | ENST00000537909.4 | |
CDH22 | XM_011528994.3 | c.1763C>T | p.Thr588Ile | missense_variant | 11/12 | ||
CDH22 | XM_047440373.1 | c.1523C>T | p.Thr508Ile | missense_variant | 9/10 | ||
CDH22 | XM_024451966.2 | c.1400C>T | p.Thr467Ile | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH22 | ENST00000537909.4 | c.1763C>T | p.Thr588Ile | missense_variant | 11/12 | 2 | NM_021248.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250450Hom.: 1 AF XY: 0.0000738 AC XY: 10AN XY: 135474
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461784Hom.: 1 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 727190
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74344
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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 | May 03, 2023 | The c.1763C>T (p.T588I) alteration is located in exon 10 (coding exon 10) of the CDH22 gene. This alteration results from a C to T substitution at nucleotide position 1763, causing the threonine (T) at amino acid position 588 to be replaced by an isoleucine (I). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of disorder (P = 0.0369);Loss of disorder (P = 0.0369);
MVP
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