5-20429236-T-C

Variant names:

• chr5-20429236-T-C
• rs10062513
• NM_001291956.3:c.-580+146226A>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+146226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,016 control chromosomes in the GnomAD database, including 3,882 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 0.22 (3882 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291956.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	NM_001291956.3		c.-580+146226A>G		intron	N/A	NP_001278885.1	Q13634-1
	CDH18	NM_001349556.2		c.-434+146226A>G		intron	N/A	NP_001336485.1	Q13634-1
	CDH18	NM_001349558.2		c.-727-90997A>G		intron	N/A	NP_001336487.1	Q13634-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000507958.5	TSL:2	c.-580+146226A>G		intron	N/A	ENSP00000425093.1	Q13634-1
	CDH18	ENST00000507632.2	TSL:4	n.402+146226A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33547 AN: 151898 Hom.: 3881 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.221 AC: 33564 AN: 152016 Hom.: 3882 Cov.: 32 AF XY: 0.219 AC XY: 16305 AN XY: 74288

African (AFR) AF: 0.198 AC: 8197 AN: 41486

American (AMR) AF: 0.139 AC: 2118 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1587 AN: 5152

South Asian (SAS) AF: 0.235 AC: 1131 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10564

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16481 AN: 67944

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.232 Hom.: 15796

Bravo AF: 0.211

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.51
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10062513;

hg19: chr5-20429345;