rs7240351

Positions:

• chr18-27974492-G-A
• chr18-27974492-G-T

Variant summary

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

The NM_001792.5(CDH2):​c.2349+8452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,044 control chromosomes in the GnomAD database, including 10,016 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 0.34 (10016 hom., cov: 32)
• Consequence: CDH2 NM_001792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH2	NM_001792.5	c.2349+8452C>T		intron_variant		ENST00000269141.8	NP_001783.2
CDH2	NM_001308176.2	c.2256+8452C>T		intron_variant			NP_001295105.1
CDH2	XM_011525788.1	c.2094+8452C>T		intron_variant			XP_011524090.1
CDH2	XM_017025514.3	c.2349+8452C>T		intron_variant			XP_016881003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8	c.2349+8452C>T		intron_variant		1	NM_001792.5	ENSP00000269141	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52096 AN: 151926 Hom.: 10017 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.343 AC: 52101 AN: 152044 Hom.: 10016 Cov.: 32 AF XY: 0.340 AC XY: 25243 AN XY: 74316

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.357

Alfa AF: 0.321 Hom.: 1305

Bravo AF: 0.322

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.72

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: rs7240351; hg19: chr18-25554456;