rs587778169

Positions:

• chr16-68737439-CT-GC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004360.5(CDH1):​c.24_25delinsGC​(p.Ser9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH1 NM_004360.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.667

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.24_25delinsGC	p.Ser9Pro	missense_variant	1/16	ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.24_25delinsGC	p.Ser9Pro	missense_variant	1/15		NP_001304113.1
CDH1	NM_001317185.2	c.-1592_-1591delinsGC		5_prime_UTR_variant	1/16		NP_001304114.1
CDH1	NM_001317186.2	c.-1796_-1795delinsGC		5_prime_UTR_variant	1/15		NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.24_25delinsGC	p.Ser9Pro	missense_variant	1/16	1	NM_004360.5	ENSP00000261769	P1
CDH1	ENST00000422392.6	c.24_25delinsGC	p.Ser9Pro	missense_variant	1/15	1		ENSP00000414946
CDH1	ENST00000566612.5	c.24_25delinsGC	p.Ser9Pro	missense_variant, NMD_transcript_variant	1/15	1		ENSP00000454782
CDH1	ENST00000566510.5	c.24_25delinsGC	p.Ser9Pro	missense_variant, NMD_transcript_variant	1/15	5		ENSP00000458139

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587778169; hg19: chr16-68771342;