rs12652510

Variant names:

• chr5-20485637-A-C
• rs12652510
• NM_001291956.3:c.-580+89825T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291956.3(CDH18):​c.-580+89825T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,048 control chromosomes in the GnomAD database, including 3,217 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 0.18 (3217 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+89825T>G		intron_variant	Intron 1 of 14		NP_001278885.1
CDH18	NM_001349556.2	c.-434+89825T>G		intron_variant	Intron 1 of 13		NP_001336485.1
CDH18	NM_001349558.2	c.-728+89825T>G		intron_variant	Intron 1 of 15		NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+89825T>G		intron_variant	Intron 1 of 14	2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+89825T>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28058 AN: 151930 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.184 AC: 28048 AN: 152048 Hom.: 3217 Cov.: 32 AF XY: 0.194 AC XY: 14409 AN XY: 74304

African (AFR) AF: 0.0708 AC: 2942 AN: 41526

American (AMR) AF: 0.285 AC: 4357 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2006 AN: 5140

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2559 AN: 10548

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13379 AN: 67952

Other (OTH) AF: 0.195 AC: 410 AN: 2106

Alfa AF: 0.191 Hom.: 722

Bravo AF: 0.181

Asia WGS AF: 0.343 AC: 1190 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12652510; hg19: chr5-20485746;