16-68833485-G-C

Variant summary

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

The NM_004360.5(CDH1):​c.2635G>C​(p.Gly879Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CDH1
NM_004360.5 missense

Scores

5
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.88
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
CDH1NM_004360.5 linkc.2635G>C p.Gly879Arg missense_variant Exon 16 of 16 ENST00000261769.10 NP_004351.1 P12830-1A0A0U2ZQU7B3GN61
CDH1NM_001317184.2 linkc.2452G>C p.Gly818Arg missense_variant Exon 15 of 15 NP_001304113.1 P12830-2B3GN61
CDH1NM_001317185.2 linkc.1087G>C p.Gly363Arg missense_variant Exon 16 of 16 NP_001304114.1 P12830B3GN61Q9UII7
CDH1NM_001317186.2 linkc.670G>C p.Gly224Arg missense_variant Exon 15 of 15 NP_001304115.1 P12830B3GN61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH1ENST00000261769.10 linkc.2635G>C p.Gly879Arg missense_variant Exon 16 of 16 1 NM_004360.5 ENSP00000261769.4 P12830-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251410
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461520
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727058
show subpopulations
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:
0.0000187
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.49
T;T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.8
L;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-4.7
D;.;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0010
D;.;D
Sift4G
Benign
0.063
T;T;T
Polyphen
1.0
D;.;.
Vest4
0.39
MutPred
0.60
Gain of solvent accessibility (P = 0.0097);.;.;
MVP
0.88
MPC
0.99
ClinPred
0.99
D
GERP RS
6.2
Varity_R
0.56
gMVP
0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200911775; hg19: chr16-68867388; API