chr5-19591065-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_004934.5(CDH18):c.991T>C(p.Leu331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,573,662 control chromosomes in the GnomAD database, including 26,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.14 ( 2024 hom., cov: 32)
Exomes 𝑓: 0.18 ( 24515 hom. )
Consequence
CDH18
NM_004934.5 synonymous
NM_004934.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.45
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP7
?
Synonymous conserved (PhyloP=1.45 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH18 | NM_004934.5 | c.991T>C | p.Leu331= | synonymous_variant | 7/13 | ENST00000382275.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH18 | ENST00000382275.6 | c.991T>C | p.Leu331= | synonymous_variant | 7/13 | 1 | NM_004934.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.144 AC: 21892AN: 151954Hom.: 2022 Cov.: 32
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GnomAD3 exomes AF: 0.170 AC: 38961AN: 229386Hom.: 3974 AF XY: 0.171 AC XY: 21335AN XY: 124566
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GnomAD4 exome AF: 0.179 AC: 253792AN: 1421590Hom.: 24515 Cov.: 27 AF XY: 0.179 AC XY: 126534AN XY: 707358
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GnomAD4 genome ? AF: 0.144 AC: 21884AN: 152072Hom.: 2024 Cov.: 32 AF XY: 0.146 AC XY: 10868AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Childhood apraxia of speech Uncertain:1
Uncertain significance, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Apr 27, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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