18-65824561-A-G

Position:

• chr18-65824561-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004361.5(CDH7):​c.794-83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 868,872 control chromosomes in the GnomAD database, including 41,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7769 hom., cov: 32)
  • Exomes 𝑓: 0.30 (33332 hom.)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-65824561-A-G is Benign according to our data. Variant chr18-65824561-A-G is described in ClinVar as [Benign]. Clinvar id is 1275553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.794-83A>G		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.794-83A>G		intron_variant
CDH7	NM_001362438.2	c.794-83A>G		intron_variant
CDH7	NM_033646.4	c.794-83A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.794-83A>G		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.794-83A>G		intron_variant		1		P1
CDH7	ENST00000536984.6	c.794-83A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47336 AN: 151652 Hom.: 7767 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.296 AC: 212001 AN: 717102 Hom.: 33332 AF XY: 0.295 AC XY: 107206 AN XY: 363836

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0290

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.312 AC: 47359 AN: 151770 Hom.: 7769 Cov.: 32 AF XY: 0.307 AC XY: 22759 AN XY: 74182

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.301

Alfa AF: 0.316 Hom.: 938

Bravo AF: 0.309

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.33

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: rs974080; hg19: chr18-63491797;