20-59958752-C-T

Variant names:

• chr20-59958752-C-T
• rs2061029502
• NM_177980.4:c.26C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177980.4(CDH26):​c.26C>T​(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH26 NM_177980.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.189
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06743118).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177980.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH26	NM_177980.4	MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 18	NP_817089.1	Q8IXH8-4
	CDH26	NR_145482.2		n.330C>T		non_coding_transcript_exon	Exon 1 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH26	ENST00000348616.9	TSL:2 MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 18	ENSP00000339390.4	Q8IXH8-4
	CDH26	ENST00000896767.1		c.26C>T	p.Pro9Leu	missense	Exon 1 of 17	ENSP00000566826.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.70
DANN	Benign	0.92
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.19
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.071
Sift	Benign	0.22	T
Sift4G	Benign	0.29	T
Vest4		0.17
MutPred		0.48		Loss of glycosylation at P9 (P = 0.0384)
MVP		0.49
MPC		0.14
ClinPred		0.11	T
GERP RS		0.064
PromoterAI		0.022	Neutral
Varity_R		0.023
gMVP		0.39
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2061029502; hg19: chr20-58533807;