Variant 16-89171853-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004933.3(CDH15):c.22G>C(p.Val8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 1,559,540 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: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

CDH15
NM_004933.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.123

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019945204).

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH15	NM_004933.3 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	1/14	ENST00000289746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDH15	ENST00000289746.3 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	1/14	1	NM_004933.3	P1
CDH15	ENST00000521087.5 linkuse as main transcript	n.87G>C		non_coding_transcript_exon_variant	1/3	5
CDH15	ENST00000524089.1 linkuse as main transcript	n.87G>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

159926

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

87116

show subpopulations

Gnomad AFR exome

AF:

0.000579

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00124

Gnomad SAS exome

AF:

0.0000423

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1407186

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

695876

show subpopulations

Gnomad4 AFR exome

AF:

0.000682

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.0000249

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000514

GnomAD4 genome

AF:

0.000184

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000238

ExAC

AF:

0.0000959

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.063

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.35

M_CAP

Benign

0.076

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.33

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Benign

0.12

Polyphen

0.022

Vest4

0.70

MVP

0.41

MPC

0.031

ClinPred

0.022

GERP RS

1.8

Varity_R

0.061

gMVP

0.36

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