18-65763104-G-A

Position:

• chr18-65763104-G-A

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.210+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,275,374 control chromosomes in the GnomAD database, including 67,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11401 hom., cov: 32)
  • Exomes 𝑓: 0.31 (56464 hom.)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.24

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=-0.78).
• BP6: Variant 18-65763104-G-A is Benign according to our data. Variant chr18-65763104-G-A is described in ClinVar as [Benign]. Clinvar id is 1243326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.210+52G>A		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.210+52G>A		intron_variant
CDH7	NM_001362438.2	c.210+52G>A		intron_variant
CDH7	NM_033646.4	c.210+52G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.210+52G>A		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.210+52G>A		intron_variant		1		P1
CDH7	ENST00000536984.6	c.210+52G>A		intron_variant		1
CDH7	ENST00000581601.1	n.45+52G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57014 AN: 151474 Hom.: 11380 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.338

GnomAD3 exomes AF: 0.354 AC: 70348 AN: 198596 Hom.: 12805 AF XY: 0.356 AC XY: 38315 AN XY: 107682

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.357

Gnomad SAS exome AF: 0.445

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.307 AC: 344898 AN: 1123782 Hom.: 56464 Cov.: 14 AF XY: 0.311 AC XY: 173948 AN XY: 558750

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.376 AC: 57067 AN: 151592 Hom.: 11401 Cov.: 32 AF XY: 0.381 AC XY: 28207 AN XY: 74054

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.337

Alfa AF: 0.336 Hom.: 2291

Bravo AF: 0.370

Asia WGS AF: 0.443 AC: 1540 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	-0.78
CADD	Benign	10
DANN	Benign	0.61

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: rs2276190; hg19: chr18-63430340;