5-20555939-C-T

Position:

• chr5-20555939-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291956.3(CDH18):​c.-580+19523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,146 control chromosomes in the GnomAD database, including 635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.059 (635 hom., cov: 31)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+19523G>A		intron_variant			NP_001278885.1
CDH18	NM_001349556.2	c.-434+19523G>A		intron_variant			NP_001336485.1
CDH18	NM_001349558.2	c.-728+19523G>A		intron_variant			NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+19523G>A		intron_variant		2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+19523G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8951 AN: 152030 Hom.: 633 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0589 AC: 8960 AN: 152146 Hom.: 635 Cov.: 31 AF XY: 0.0579 AC XY: 4309 AN XY: 74394

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0159 Hom.: 15

Bravo AF: 0.0635

Asia WGS AF: 0.0430 AC: 149 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.060
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10520867; hg19: chr5-20556048;