chr18-65763108-T-C

Variant names:

• chr18-65763108-T-C
• rs2276191
• NM_004361.5:c.210+56T>C

Variant summary

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

The NM_004361.5(CDH7):​c.210+56T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 4 publications found

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

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 (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.210+56T>C		intron_variant	Intron 2 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.210+56T>C		intron_variant	Intron 2 of 11		NP_001349367.1
CDH7	NM_033646.4	c.210+56T>C		intron_variant	Intron 2 of 11		NP_387450.1
CDH7	NM_001317214.3	c.210+56T>C		intron_variant	Intron 2 of 10		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.210+56T>C		intron_variant	Intron 2 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.210+56T>C		intron_variant	Intron 2 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.210+56T>C		intron_variant	Intron 2 of 10	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.45+56T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		0.14

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: rs2276191; hg19: chr18-63430344;