Variant 18-61528140-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031891.4(CDH20):c.1191G>C(p.Glu397Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDH20
NM_031891.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

CDH20 (HGNC:1760): (cadherin 20) This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. [provided by RefSeq, Jul 2008]

CDH20 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40386838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH20	NM_031891.4 link	c.1191G>C	p.Glu397Asp	missense_variant	7/12	ENST00000262717.9	NP_114097.2	Q9HBT6A8K2C5Q8N9J3
CDH20	XM_024451165.2 link	c.1191G>C	p.Glu397Asp	missense_variant	7/12		XP_024306933.1
CDH20	XR_001753186.2 link	n.1741G>C		non_coding_transcript_exon_variant	7/11
CDH20	XR_001753187.2 link	n.1741G>C		non_coding_transcript_exon_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDH20	ENST00000262717.9 link	c.1191G>C	p.Glu397Asp	missense_variant	7/12	2	NM_031891.4	ENSP00000262717.3	Q9HBT6
CDH20	ENST00000536675.2 link	c.1191G>C	p.Glu397Asp	missense_variant	6/11	1		ENSP00000444767.1	Q9HBT6
CDH20	ENST00000538374.5 link	c.1191G>C	p.Glu397Asp	missense_variant	7/12	1		ENSP00000442226.1	Q9HBT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

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:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2022

The c.1191G>C (p.E397D) alteration is located in exon 6 (coding exon 6) of the CDH20 gene. This alteration results from a G to C substitution at nucleotide position 1191, causing the glutamic acid (E) at amino acid position 397 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T;T

Eigen

Benign

-0.058

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

.;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.079

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.25

B;B;B

Vest4

0.61

MutPred

0.48

Loss of phosphorylation at Y394 (P = 0.0968);Loss of phosphorylation at Y394 (P = 0.0968);Loss of phosphorylation at Y394 (P = 0.0968);

MVP

0.92

MPC

0.48

ClinPred

0.87

GERP RS

4.0

Varity_R

0.15

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over