rs13689

Variant names:

• chr16-68834619-T-C
• rs13689
• NM_004360.5:c.*1120T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-68834619-T-C
• chr16-68834619-T-A
• chr16-68834619-T-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP2 BA1

This summary comes from the ClinGen Evidence Repository: The NM_004360.5(CDH1):c.*1120T>C variant has an allele frequency of 0.21013 (21%, 730/3474 alleles, 79 homozygotes) in the African subpopulation of the gnomAD v2.1.1 cohort (BA1; BP2). Therefore, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BP2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10647981/MONDO:0007648/007

• Frequency:
  • Genomes: 𝑓 0.18 (2356 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1398 hom.)
• Consequence: CDH1 NM_004360.5 3_prime_UTR
• Clinical Significance: Benign reviewed by expert panel B:3
• Conservation: PhyloP100: -0.682
• Publications: 27 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, Labcorp Genetics (formerly Invitae), G2P, Illumina
• CDH1-related diffuse gastric and lobular breast cancer syndrome

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

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

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• 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: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP2: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH1	NM_004360.5	MANE Select	c.*1120T>C		3_prime_UTR	Exon 16 of 16	NP_004351.1	A0A0U2ZQU7
	CDH1	NM_001317184.2		c.*1120T>C		3_prime_UTR	Exon 15 of 15	NP_001304113.1	P12830-2
	CDH1	NM_001317185.2		c.*1120T>C		3_prime_UTR	Exon 16 of 16	NP_001304114.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH1	ENST00000261769.10	TSL:1 MANE Select	c.*1120T>C		3_prime_UTR	Exon 16 of 16	ENSP00000261769.4	P12830-1
	CDH1	ENST00000566612.5	TSL:1	n.*2009T>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000454782.1	H3BNC6
	CDH1	ENST00000566612.5	TSL:1	n.*2009T>C		3_prime_UTR	Exon 15 of 15	ENSP00000454782.1	H3BNC6

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27019 AN: 152114 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.170 AC: 15218 AN: 89672 Hom.: 1398 Cov.: 0 AF XY: 0.168 AC XY: 7101 AN XY: 42196

African (AFR) AF: 0.159 AC: 618 AN: 3878

American (AMR) AF: 0.175 AC: 515 AN: 2950

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 884 AN: 5078

East Asian (EAS) AF: 0.128 AC: 1424 AN: 11102

South Asian (SAS) AF: 0.0896 AC: 223 AN: 2488

European-Finnish (FIN) AF: 0.190 AC: 177 AN: 932

Middle Eastern (MID) AF: 0.168 AC: 86 AN: 512

European-Non Finnish (NFE) AF: 0.181 AC: 10060 AN: 55640

Other (OTH) AF: 0.174 AC: 1231 AN: 7092

GnomAD4 genome AF: 0.178 AC: 27063 AN: 152232 Hom.: 2356 Cov.: 32 AF XY: 0.177 AC XY: 13165 AN XY: 74444

African (AFR) AF: 0.153 AC: 6338 AN: 41544

American (AMR) AF: 0.179 AC: 2742 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.156 AC: 808 AN: 5180

South Asian (SAS) AF: 0.111 AC: 535 AN: 4832

European-Finnish (FIN) AF: 0.212 AC: 2248 AN: 10594

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13225 AN: 68008

Other (OTH) AF: 0.167 AC: 351 AN: 2108

Alfa AF: 0.185 Hom.: 1271

Bravo AF: 0.179

Asia WGS AF: 0.150 AC: 519 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	1	CDH1-related diffuse gastric and lobular breast cancer syndrome (1)
-	-	1	Hereditary diffuse gastric adenocarcinoma (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.52
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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: rs13689; hg19: chr16-68868522; COSMIC: COSV55740499; COSMIC: COSV55740499;