chr18-65814579-G-A

Variant names:

• chr18-65814579-G-A
• rs17075245
• NM_004361.5:c.600G>A

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.600G>A​(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,612,964 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.16
• 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=-0.77).
• BP6: Variant 18-65814579-G-A is Benign according to our data. Variant chr18-65814579-G-A is described in ClinVar as [Benign]. Clinvar id is 790743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 12		NP_001349367.1
CDH7	NM_033646.4	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 12		NP_387450.1
CDH7	NM_001317214.3	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.600G>A	p.Pro200Pro	synonymous_variant	Exon 4 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2445 AN: 151978 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00414 AC: 1037 AN: 250656 AF XY: 0.00302

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.00218

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00165 AC: 2416 AN: 1460868 Hom.: 64 Cov.: 30 AF XY: 0.00140 AC XY: 1015 AN XY: 726752

African (AFR) AF: 0.0543 AC: 1817 AN: 33442

American (AMR) AF: 0.00262 AC: 117 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000395 AC: 34 AN: 86116

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5758

European-Non Finnish (NFE) AF: 0.000181 AC: 201 AN: 1111442

Other (OTH) AF: 0.00376 AC: 227 AN: 60344

GnomAD4 genome AF: 0.0161 AC: 2446 AN: 152096 Hom.: 53 Cov.: 32 AF XY: 0.0159 AC XY: 1179 AN XY: 74356

African (AFR) AF: 0.0548 AC: 2273 AN: 41470

American (AMR) AF: 0.00804 AC: 123 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67986

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00604 Hom.: 39

Bravo AF: 0.0181

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.00

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

- -

Jun 27, 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	-0.77
CADD	Benign	0.057
DANN	Benign	0.70
PhyloP100		-3.2
Mutation Taster		=97/3	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: rs17075245; hg19: chr18-63481815;