NM_001792.5:c.60+5261C>T

Variant names:

• chr18-28171702-G-A
• rs12605662
• NM_001792.5:c.60+5261C>T

Variant summary

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

The NM_001792.5(CDH2):​c.60+5261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,002 control chromosomes in the GnomAD database, including 19,846 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 0.49 (19846 hom., cov: 32)
• Consequence: CDH2 NM_001792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH2	NM_001792.5	MANE Select	c.60+5261C>T		intron	N/A	NP_001783.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH2	ENST00000269141.8	TSL:1 MANE Select	c.60+5261C>T		intron	N/A	ENSP00000269141.3
	CDH2	ENST00000430882.6	TSL:4	c.-388+5261C>T		intron	N/A	ENSP00000412120.2
	CDH2	ENST00000676445.1		c.-196+6161C>T		intron	N/A	ENSP00000502206.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73982 AN: 151884 Hom.: 19839 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.487 AC: 74004 AN: 152002 Hom.: 19846 Cov.: 32 AF XY: 0.491 AC XY: 36443 AN XY: 74264

African (AFR) AF: 0.242 AC: 10039 AN: 41416

American (AMR) AF: 0.549 AC: 8387 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2251 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3317 AN: 5158

South Asian (SAS) AF: 0.559 AC: 2694 AN: 4816

European-Finnish (FIN) AF: 0.568 AC: 5996 AN: 10550

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39410 AN: 67990

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

Alfa AF: 0.550 Hom.: 19390

Bravo AF: 0.476

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.60
PhyloP100		-0.42
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: rs12605662; hg19: chr18-25751666;