ENST00000566612.5:n.-8G>A

Variant names:

• chr16-68737304-A-.
• NM_004360.5:c.-112A>.

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000566612.5(CDH1):​n.-112A>. variant causes a upstream gene change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 N/A (N/A hom., cov:)
  • Exomes 𝑓: N/A (N/A hom.)
• Consequence: CDH1 ENST00000566612.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: No publications found

Genes affected

CDH1 (HGNC:1748): (cadherin 1) 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. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

CDH1 Gene-Disease associations (from GenCC):

• blepharocheilodontic syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P
• CDH1-related diffuse gastric and lobular breast cancer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• hereditary diffuse gastric adenocarcinoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• cleft soft palate

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• orofacial cleft 3

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• blepharocheilodontic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH1	NM_004360.5	c.-112A>.		5_prime_UTR_variant	Exon 1 of 16	ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.-112A>.		5_prime_UTR_variant	Exon 1 of 15		NP_001304113.1
CDH1	NM_001317185.2	c.-1727A>.		5_prime_UTR_variant	Exon 1 of 16		NP_001304114.1
CDH1	NM_001317186.2	c.-1931A>.		5_prime_UTR_variant	Exon 1 of 15		NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.-112A>.		5_prime_UTR_variant	Exon 1 of 16	1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.-112A>.		upstream_gene_variant		1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.-112A>.		upstream_gene_variant		1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.-112A>.		upstream_gene_variant		5		ENSP00000458139.1

Frequencies

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Other links and lift over

hg19: chr16-68771207;