Variant 18-66505086-T-A 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_021153.4(CDH19):c.2045A>T(p.Tyr682Phe) 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 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDH19
NM_021153.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

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:

CDH19 (HGNC:):

CDH19 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=0.22266105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH19	NM_021153.4 linkuse as main transcript	c.2045A>T	p.Tyr682Phe	missense_variant	12/12	ENST00000262150.7	NP_066976.1	Q9H159-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDH19	ENST00000262150.7 linkuse as main transcript	c.2045A>T	p.Tyr682Phe	missense_variant	12/12	1	NM_021153.4	ENSP00000262150.2	Q9H159-1
CDH19	ENST00000579658.5 linkuse as main transcript	n.*391A>T		non_coding_transcript_exon_variant	12/12	1		ENSP00000463085.1	J3KTP3
CDH19	ENST00000579658.5 linkuse as main transcript	n.*391A>T		3_prime_UTR_variant	12/12	1		ENSP00000463085.1	J3KTP3
CDH19	ENST00000540086 linkuse as main transcript	c.*202A>T		3_prime_UTR_variant	10/10	2		ENSP00000439593.1	Q9H159-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

0.00

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

Jan 02, 2024

The c.2045A>T (p.Y682F) alteration is located in exon 12 (coding exon 11) of the CDH19 gene. This alteration results from a A to T substitution at nucleotide position 2045, causing the tyrosine (Y) at amino acid position 682 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0068

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.84

M_CAP

Benign

0.063

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.88

REVEL

Benign

0.27

Sift

Benign

0.62

Sift4G

Benign

0.68

Polyphen

0.61

Vest4

0.079

MutPred

0.63

Gain of disorder (P = 0.0769);

MVP

0.87

MPC

0.12

ClinPred

0.38

GERP RS

4.0

Varity_R

0.11

gMVP

0.17

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