Variant rs587782484 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004360.5(CDH1):c.8C>A(p.Pro3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CDH1
NM_004360.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

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]

CDH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20828602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH1	NM_004360.5 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant	1/16	ENST00000261769.10
CDH1	NM_001317184.2 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant	1/15
CDH1	NM_001317185.2 linkuse as main transcript	c.-1608C>A		5_prime_UTR_variant	1/16
CDH1	NM_001317186.2 linkuse as main transcript	c.-1812C>A		5_prime_UTR_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH1	ENST00000261769.10 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant	1/16	1	NM_004360.5	P1	P12830-1
CDH1	ENST00000422392.6 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant	1/15	1			P12830-2
CDH1	ENST00000566612.5 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant, NMD_transcript_variant	1/15	1
CDH1	ENST00000566510.5 linkuse as main transcript	c.8C>A	p.Pro3His	missense_variant, NMD_transcript_variant	1/15	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000775

AC:

AN:

129088

Hom.:

AF XY:

0.0000141

AC XY:

AN XY:

71060

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:

0.0000451

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1381820

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682176

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:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000110

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T;T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.59

T;T;T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.;.;.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

N;.;.;.;N

REVEL

Benign

0.058

Sift

Uncertain

0.0030

D;.;.;.;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.91

P;.;.;.;.

Vest4

0.55

MutPred

0.40

Gain of MoRF binding (P = 0.0203);Gain of MoRF binding (P = 0.0203);Gain of MoRF binding (P = 0.0203);Gain of MoRF binding (P = 0.0203);Gain of MoRF binding (P = 0.0203);

MVP

0.81

MPC

0.97

ClinPred

0.62

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over