rs2426865

Positions:

• chr20-59997172-T-A

Variant summary

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

The NM_177980.4(CDH26):​c.2019+411T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,242 control chromosomes in the GnomAD database, including 7,272 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 0.19 (7272 hom., cov: 33)
• Consequence: CDH26 NM_177980.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

CDH26 (HGNC:15902): (cadherin 26) This gene encodes a member of the cadherin protein family. Cadherins are a family of calcium-dependent adhesion molecules that mediate cell-cell adhesion in all solid tissues and modulate a wide variety of processes, including cell polarization, migration and differentiation. Cadherin domains occur as repeats in the extracellular region and are thought to contribute to the sorting of heterogeneous cell types and the maintenance of orderly structures such as epithelium. This protein is expressed in gastrointestinal epithelial cells and may be upregulated during allergic inflammation. This protein interacts with alpha integrins and may also be involved in leukocyte migration and adhesion. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH26	NM_177980.4	c.2019+411T>A		intron_variant		ENST00000348616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH26	ENST00000348616.9	c.2019+411T>A		intron_variant		2	NM_177980.4	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29368 AN: 152124 Hom.: 7227 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.194 AC: 29476 AN: 152242 Hom.: 7272 Cov.: 33 AF XY: 0.189 AC XY: 14054 AN XY: 74438

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.156

Alfa AF: 0.128 Hom.: 545

Bravo AF: 0.214

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.63

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: rs2426865; hg19: chr20-58572227;