18-28171702-G-A

Position:

• chr18-28171702-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH2	NM_001792.5	c.60+5261C>T		intron_variant		ENST00000269141.8	NP_001783.2
CDH2	XM_017025514.3	c.60+5261C>T		intron_variant			XP_016881003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8	c.60+5261C>T		intron_variant		1	NM_001792.5	ENSP00000269141	P1

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

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.567

Alfa AF: 0.550 Hom.: 16314

Bravo AF: 0.476

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.60

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: rs12605662; hg19: chr18-25751666;