chr18-65762848-G-A

Variant names:

• chr18-65762848-G-A
• rs114985920
• NM_004361.5:c.6G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004361.5(CDH7):​c.6G>A​(p.Lys2Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,605,906 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: CDH7 NM_004361.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.51
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 18-65762848-G-A is Benign according to our data. Variant chr18-65762848-G-A is described in ClinVar as [Benign]. Clinvar id is 714874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.51 with no splicing effect.
• BS2: High AC in GnomAd4 at 443 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 12		NP_387450.1
CDH7	NM_001317214.3	c.6G>A	p.Lys2Lys	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.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 2 of 11	1		ENSP00000443030.2
CDH7	ENST00000581601.1	n.-160G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 437 AN: 152086 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000761 AC: 186 AN: 244296 AF XY: 0.000464

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.000503

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000287 AC: 417 AN: 1453702 Hom.: 2 Cov.: 32 AF XY: 0.000245 AC XY: 177 AN XY: 722522

African (AFR) AF: 0.00905 AC: 299 AN: 33050

American (AMR) AF: 0.000546 AC: 24 AN: 43920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000479 AC: 4 AN: 83470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5028

European-Non Finnish (NFE) AF: 0.0000433 AC: 48 AN: 1109390

Other (OTH) AF: 0.000700 AC: 42 AN: 59992

GnomAD4 genome AF: 0.00291 AC: 443 AN: 152204 Hom.: 3 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74416

African (AFR) AF: 0.0104 AC: 432 AN: 41530

American (AMR) AF: 0.000458 AC: 7 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00137 Hom.: 1

Bravo AF: 0.00323

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		3.5
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114985920; hg19: chr18-63430084; COSMIC: COSV106443939; COSMIC: COSV106443939;