18-65762926-A-G

Variant names:

• chr18-65762926-A-G
• rs7229292
• NM_004361.5:c.84A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004361.5(CDH7):​c.84A>G​(p.Glu28Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,538 control chromosomes in the GnomAD database, including 379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (190 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (189 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.523
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 18-65762926-A-G is Benign according to our data. Variant chr18-65762926-A-G is described in ClinVar as [Benign]. Clinvar id is 773074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.523 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 12		NP_387450.1
CDH7	NM_001317214.3	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.84A>G	p.Glu28Glu	synonymous_variant	Exon 2 of 11	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.-82A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4271 AN: 151984 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0216

GnomAD2 exomes AF: 0.00757 AC: 1903 AN: 251238 AF XY: 0.00558

Gnomad AFR exome AF: 0.0983

Gnomad AMR exome AF: 0.00681

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00302 AC: 4419 AN: 1461436 Hom.: 189 Cov.: 32 AF XY: 0.00266 AC XY: 1937 AN XY: 727054

African (AFR) AF: 0.100 AC: 3355 AN: 33440

American (AMR) AF: 0.00725 AC: 324 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00547 AC: 31 AN: 5664

European-Non Finnish (NFE) AF: 0.000212 AC: 236 AN: 1111798

Other (OTH) AF: 0.00760 AC: 459 AN: 60366

GnomAD4 genome AF: 0.0282 AC: 4284 AN: 152102 Hom.: 190 Cov.: 32 AF XY: 0.0264 AC XY: 1961 AN XY: 74356

African (AFR) AF: 0.0961 AC: 3985 AN: 41480

American (AMR) AF: 0.0148 AC: 226 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67998

Other (OTH) AF: 0.0214 AC: 45 AN: 2106

Alfa AF: 0.00968 Hom.: 100

Bravo AF: 0.0331

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs7229292; hg19: chr18-63430162;