chr16-68737444-CGCTGCT-C

Position:

• chr16-68737444-CGCTGCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_004360.5(CDH1):​c.41_46delTGCTGC​(p.Leu14_Leu15del) variant causes a disruptive inframe deletion, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CDH1 NM_004360.5 disruptive_inframe_deletion, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-68737444-CGCTGCT-C is Benign according to our data. Variant chr16-68737444-CGCTGCT-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.41_46delTGCTGC	p.Leu14_Leu15del	disruptive_inframe_deletion, splice_region_variant	1/16	ENST00000261769.10	NP_004351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.41_46delTGCTGC	p.Leu14_Leu15del	disruptive_inframe_deletion, splice_region_variant	1/16	1	NM_004360.5	ENSP00000261769.4
CDH1	ENST00000422392.6	c.41_46delTGCTGC	p.Leu14_Leu15del	disruptive_inframe_deletion, splice_region_variant	1/15	1		ENSP00000414946.2
CDH1	ENST00000566612.5	n.41_46delTGCTGC		splice_region_variant, non_coding_transcript_exon_variant	1/15	1		ENSP00000454782.1
CDH1	ENST00000566510.5	n.41_46delTGCTGC		splice_region_variant, non_coding_transcript_exon_variant	1/15	5		ENSP00000458139.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1337636 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 661382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.61e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-68771347;