18-28093911-C-T

Variant names:

• chr18-28093911-C-T
• rs528438
• NM_001792.5:c.172+53762G>A

Variant summary

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

The NM_001792.5(CDH2):​c.172+53762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,994 control chromosomes in the GnomAD database, including 33,455 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 0.65 (33455 hom., cov: 31)
• Consequence: CDH2 NM_001792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 6 publications found

Genes affected

CDH2 (HGNC:1759): (cadherin 2) This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone. [provided by RefSeq, Nov 2015]

CDH2 Gene-Disease associations (from GenCC):

• agenesis of corpus callosum, cardiac, ocular, and genital syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• arrhythmogenic right ventricular dysplasia, familial, 14

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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 (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001792.5. 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
	CDH2	NM_001792.5	MANE Select	c.172+53762G>A		intron	N/A	NP_001783.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH2	ENST00000269141.8	TSL:1 MANE Select	c.172+53762G>A		intron	N/A	ENSP00000269141.3	P19022-1
	CDH2	ENST00000876838.1		c.172+53762G>A		intron	N/A	ENSP00000546897.1
	CDH2	ENST00000876839.1		c.172+53762G>A		intron	N/A	ENSP00000546898.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99035 AN: 151876 Hom.: 33414 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.652 AC: 99133 AN: 151994 Hom.: 33455 Cov.: 31 AF XY: 0.640 AC XY: 47527 AN XY: 74280

African (AFR) AF: 0.711 AC: 29479 AN: 41448

American (AMR) AF: 0.555 AC: 8474 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2048 AN: 3472

East Asian (EAS) AF: 0.176 AC: 911 AN: 5166

South Asian (SAS) AF: 0.446 AC: 2153 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6658 AN: 10548

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47195 AN: 67956

Other (OTH) AF: 0.646 AC: 1364 AN: 2112

Alfa AF: 0.667 Hom.: 54525

Bravo AF: 0.645

Asia WGS AF: 0.385 AC: 1340 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	0.0010
DANN	Benign	0.70
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs528438; hg19: chr18-25673875;