rs1886699

Variant names:

• chr16-68698554-G-A
• rs1886699
• NM_001793.6:c.*154G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-68698554-G-A
• chr16-68698554-G-C
• chr16-68698554-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001793.6(CDH3):​c.*154G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDH3 NM_001793.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 19 publications found

Genes affected

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]

CDH3 Gene-Disease associations (from GenCC):

• EEM syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital hypotrichosis with juvenile macular dystrophy

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001793.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	NM_001793.6	MANE Select	c.*154G>A		3_prime_UTR	Exon 16 of 16	NP_001784.2
	CDH3	NM_001317195.3		c.*387G>A		3_prime_UTR	Exon 16 of 16	NP_001304124.1
	CDH3	NM_001317196.2		c.*154G>A		3_prime_UTR	Exon 15 of 15	NP_001304125.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	ENST00000264012.9	TSL:1 MANE Select	c.*154G>A		3_prime_UTR	Exon 16 of 16	ENSP00000264012.4
	CDH3	ENST00000429102.6	TSL:1	c.*387G>A		3_prime_UTR	Exon 16 of 16	ENSP00000398485.2
	CDH3	ENST00000542274.5	TSL:2	n.*2382G>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000464021.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 505830 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 265740

African (AFR) AF: 0.00 AC: 0 AN: 13738

American (AMR) AF: 0.00 AC: 0 AN: 22704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14730

East Asian (EAS) AF: 0.00 AC: 0 AN: 31620

South Asian (SAS) AF: 0.00 AC: 0 AN: 48630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 307910

Other (OTH) AF: 0.00 AC: 0 AN: 27984

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.81
PhyloP100		-2.6

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: rs1886699; hg19: chr16-68732457;