Variant rs121434539 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2

The ENST00000289746.3(CDH15):c.178C>T(p.Arg60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,606,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CDH15
ENST00000289746.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 0.671

Variant links:

Genes affected

CDH15 (HGNC:1754): (cadherin 15) This gene is a member of the cadherin superfamily of genes, encoding calcium-dependent intercellular adhesion glycoproteins. Cadherins consist of an extracellular domain containing 5 cadherin domains, a transmembrane region, and a conserved cytoplasmic domain. Transcripts from this particular cadherin are expressed in myoblasts and upregulated in myotubule-forming cells. The protein is thought to be essential for the control of morphogenetic processes, specifically myogenesis, and may provide a trigger for terminal muscle cell differentiation. [provided by RefSeq, Jul 2008]

CDH15 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=0.33291668).

BP6

Variant 16-89179551-C-T is Benign according to our data. Variant chr16-89179551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 17642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH15	NM_004933.3 linkuse as main transcript	c.178C>T	p.Arg60Cys	missense_variant	2/14	ENST00000289746.3	NP_004924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDH15	ENST00000289746.3 linkuse as main transcript	c.178C>T	p.Arg60Cys	missense_variant	2/14	1	NM_004933.3	ENSP00000289746	P1
CDH15	ENST00000521087.5 linkuse as main transcript	n.243C>T		non_coding_transcript_exon_variant	2/3	5
CDH15	ENST00000524089.1 linkuse as main transcript	n.243C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

245476

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

132780

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000887

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000509

AC:

AN:

1454434

Hom.:

Cov.:

AF XY:

0.0000609

AC XY:

AN XY:

722864

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000195

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 3

Pathogenic:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 19, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 01, 2008	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 18, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

0.098

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.58

MVP

0.84

MPC

0.22

ClinPred

0.27

GERP RS

0.81

Varity_R

0.49

gMVP

0.61

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