5-19483313-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004934.5(CDH18):c.1870C>T(p.Leu624Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L624I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CDH18
NM_004934.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

4 publications found

Variant links:

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]

CDH18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11599517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004934.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH18	NM_004934.5	MANE Select	c.1870C>T	p.Leu624Phe	missense	Exon 12 of 13	NP_004925.1	Q13634-1
CDH18	NM_001291956.3		c.1870C>T	p.Leu624Phe	missense	Exon 14 of 15	NP_001278885.1	Q13634-1
CDH18	NM_001349556.2		c.1870C>T	p.Leu624Phe	missense	Exon 13 of 14	NP_001336485.1	Q13634-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH18	ENST00000382275.6	TSL:1 MANE Select	c.1870C>T	p.Leu624Phe	missense	Exon 12 of 13	ENSP00000371710.1	Q13634-1
CDH18	ENST00000274170.8	TSL:1	c.1870C>T	p.Leu624Phe	missense	Exon 10 of 11	ENSP00000274170.3	Q13634-1
CDH18	ENST00000506372.5	TSL:1	c.*36C>T		3_prime_UTR	Exon 12 of 13	ENSP00000424931.1	D6RER2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250198

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460912

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726718

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111492

Other (OTH)

AF:

0.0000166

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.062

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.85

M_CAP

Benign

0.021

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

-0.84

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.83

REVEL

Benign

0.12

Sift

Benign

0.33

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.37

MutPred

0.54

Loss of catalytic residue at L624 (P = 0.0875)

MVP

0.41

MPC

0.15

ClinPred

0.095

GERP RS

1.2

Varity_R

0.11

gMVP

0.60

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over