rs147397532

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004933.3(CDH15):c.2146A>G(p.Asn716Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000633 in 1,611,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CDH15
NM_004933.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.430

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019061387).

BP6

Variant 16-89193908-A-G is Benign according to our data. Variant chr16-89193908-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210627.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH15	NM_004933.3 link	c.2146A>G	p.Asn716Asp	missense_variant	Exon 13 of 14	ENST00000289746.3	NP_004924.1	P55291

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH15	ENST00000289746.3 link	c.2146A>G	p.Asn716Asp	missense_variant	Exon 13 of 14	1	NM_004933.3	ENSP00000289746.2		P55291

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000792

AC:

AN:

239968

Hom.:

AF XY:

0.0000532

AC XY:

AN XY:

131670

show subpopulations

Gnomad AFR exome

AF:

0.000607

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000850

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1459822

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726216

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000179

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:

0.00000989

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000349

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000966

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.000690

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.000133

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Aug 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2146A>G (p.N716D) alteration is located in exon 13 (coding exon 13) of the CDH15 gene. This alteration results from a A to G substitution at nucleotide position 2146, causing the asparagine (N) at amino acid position 716 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Aug 09, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.15

M_CAP

Benign

0.028

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

REVEL

Benign

0.23

Sift

Benign

0.81

Sift4G

Benign

0.34

Polyphen

0.023

Vest4

0.20

MVP

0.56

MPC

0.13

ClinPred

0.013

GERP RS

0.40

Varity_R

0.12

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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