16-68644752-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000562172.2(CDH3-AS1):n.1178C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDH3-AS1 ENST00000562172.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.564

Genes affected

CDH3-AS1 (HGNC:56084): (CDH3 antisense RNA 1)

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a 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 protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH3-AS1	ENST00000562172.2	n.1178C>T		non_coding_transcript_exon_variant	2/2	3
CDH3	ENST00000565453.1	n.223-257G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 246 AN: 130610 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000763

Gnomad ASJ AF: 0.00357

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.000511

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00746

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00401

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00140 AC: 1 AN: 712 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00192 AC: 251 AN: 130640 Hom.: 0 Cov.: 32 AF XY: 0.00244 AC XY: 154 AN XY: 63170

Gnomad4 AFR AF: 0.000214

Gnomad4 AMR AF: 0.000686

Gnomad4 ASJ AF: 0.00357

Gnomad4 EAS AF: 0.00414

Gnomad4 SAS AF: 0.000768

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.00511

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

EEM syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.2
Dann	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs796187375; hg19: chr16-68678655; COSMIC: COSV50554765;