Variant 18-66505173-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_021153.4(CDH19):c.1958C>A(p.Ala653Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,613,228 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00057 ( 3 hom. )

Consequence

CDH19
NM_021153.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 9.33

Variant links:

Genes affected

CDH19 (HGNC:1758): (cadherin 19) This gene is one of three related type II cadherin genes situated in a cluster on chromosome 18. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein containing five extracellular cadherin repeats. Loss of cadherins may be associated with cancer formation. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Aug 2012]

CDH19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014622867).

BP6

Variant 18-66505173-G-T is Benign according to our data. Variant chr18-66505173-G-T is described in ClinVar as [Benign]. Clinvar id is 3056634.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000571 (835/1461172) while in subpopulation AFR AF= 0.0168 (561/33414). AF 95% confidence interval is 0.0156. There are 3 homozygotes in gnomad4_exome. There are 366 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH19	NM_021153.4 linkuse as main transcript	c.1958C>A	p.Ala653Asp	missense_variant	12/12	ENST00000262150.7	NP_066976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH19	ENST00000262150.7 linkuse as main transcript	c.1958C>A	p.Ala653Asp	missense_variant	12/12	1	NM_021153.4	ENSP00000262150	P1	Q9H159-1
CDH19	ENST00000579658.5 linkuse as main transcript	c.*304C>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	1		ENSP00000463085
CDH19	ENST00000540086.5 linkuse as main transcript	c.*115C>A		3_prime_UTR_variant	10/10	2		ENSP00000439593		Q9H159-2

Frequencies

GnomAD3 genomes

AF:

0.00469

AC:

712

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00230

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00119

AC:

299

AN:

250668

Hom.:

AF XY:

0.000945

AC XY:

128

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000571

AC:

835

AN:

1461172

Hom.:

Cov.:

AF XY:

0.000503

AC XY:

366

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00470

AC:

715

AN:

152056

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

344

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.00230

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000793

Hom.:

Bravo

AF:

0.00564

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00144

AC:

175

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDH19-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.015

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.91

MVP

1.0

MPC

0.31

ClinPred

0.050

GERP RS

5.2

Varity_R

0.89

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over