rs1148374

Positions:

• chr18-28070318-T-A

Variant summary

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

The NM_001792.5(CDH2):​c.173-56409A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,132 control chromosomes in the GnomAD database, including 8,638 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 0.31 (8638 hom., cov: 32)
• Consequence: CDH2 NM_001792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH2	NM_001792.5	c.173-56409A>T		intron_variant		ENST00000269141.8
CDH2	XM_011525788.1	c.-83-56409A>T		intron_variant
CDH2	XM_017025514.3	c.173-56409A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH2	ENST00000269141.8	c.173-56409A>T		intron_variant		1	NM_001792.5	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46745 AN: 152014 Hom.: 8635 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.307 AC: 46755 AN: 152132 Hom.: 8638 Cov.: 32 AF XY: 0.304 AC XY: 22628 AN XY: 74374

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.344

Alfa AF: 0.365 Hom.: 1400

Bravo AF: 0.287

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1148374; hg19: chr18-25650282;