chr18-65763104-G-A

Variant names:

• chr18-65763104-G-A
• rs2276190
• NM_004361.5:c.210+52G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.210+52G>A		intron_variant	Intron 2 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.210+52G>A		intron_variant	Intron 2 of 11		NP_001349367.1
CDH7	NM_033646.4	c.210+52G>A		intron_variant	Intron 2 of 11		NP_387450.1
CDH7	NM_001317214.3	c.210+52G>A		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+52G>A		intron_variant	Intron 2 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.210+52G>A		intron_variant	Intron 2 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.210+52G>A		intron_variant	Intron 2 of 10	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.45+52G>A		intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.354 AC: 70348 AN: 198596 AF XY: 0.356

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 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

African (AFR) AF: 0.534 AC: 13792 AN: 25846

American (AMR) AF: 0.301 AC: 9239 AN: 30688

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 5847 AN: 20678

East Asian (EAS) AF: 0.347 AC: 12763 AN: 36760

South Asian (SAS) AF: 0.442 AC: 25492 AN: 57730

European-Finnish (FIN) AF: 0.394 AC: 19012 AN: 48196

Middle Eastern (MID) AF: 0.406 AC: 1358 AN: 3346

European-Non Finnish (NFE) AF: 0.284 AC: 241991 AN: 853190

Other (OTH) AF: 0.325 AC: 15404 AN: 47348

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

African (AFR) AF: 0.519 AC: 21406 AN: 41280

American (AMR) AF: 0.297 AC: 4525 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3464

East Asian (EAS) AF: 0.344 AC: 1764 AN: 5132

South Asian (SAS) AF: 0.442 AC: 2128 AN: 4818

European-Finnish (FIN) AF: 0.411 AC: 4299 AN: 10470

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20770 AN: 67902

Other (OTH) AF: 0.337 AC: 708 AN: 2100

Alfa AF: 0.343 Hom.: 3961

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

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

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	-0.78
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		2.2
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: rs2276190; hg19: chr18-63430340;