rs8087457

Positions:

• chr18-28037661-A-C
• chr18-28037661-A-T

Variant summary

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

The NM_001792.5(CDH2):​c.173-23752T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,020 control chromosomes in the GnomAD database, including 16,461 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 0.46 (16461 hom., cov: 32)
• Consequence: CDH2 NM_001792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH2	NM_001792.5	c.173-23752T>G		intron_variant		ENST00000269141.8
CDH2	XM_011525788.1	c.-83-23752T>G		intron_variant
CDH2	XM_017025514.3	c.173-23752T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH2	ENST00000269141.8	c.173-23752T>G		intron_variant		1	NM_001792.5	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69956 AN: 151902 Hom.: 16450 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.460 AC: 69998 AN: 152020 Hom.: 16461 Cov.: 32 AF XY: 0.461 AC XY: 34275 AN XY: 74284

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.470

Alfa AF: 0.462 Hom.: 7241

Bravo AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.043
DANN	Benign	0.24

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: rs8087457; hg19: chr18-25617625;