dbSNP rs779470688: CDH15:p.Gly599Asp (chr16-89192385-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004933.3(CDH15):c.1796G>A(p.Gly599Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,385,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G599V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

CDH15
NM_004933.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, autosomal dominant 3
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
intellectual disability
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CDH15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004933.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH15	NM_004933.3	MANE Select	c.1796G>A	p.Gly599Asp	missense	Exon 11 of 14	NP_004924.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDH15	ENST00000289746.3	TSL:1 MANE Select	c.1796G>A	p.Gly599Asp	missense	Exon 11 of 14	ENSP00000289746.2
CDH15	ENST00000967215.1		c.1796G>A	p.Gly599Asp	missense	Exon 11 of 14	ENSP00000637274.1
CDH15	ENST00000859655.1		c.1646G>A	p.Gly549Asp	missense	Exon 11 of 14	ENSP00000529714.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000753

AC:

AN:

132768

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000505

AC:

AN:

1385814

Hom.:

Cov.:

AF XY:

0.00000877

AC XY:

AN XY:

684382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31676

American (AMR)

AF:

0.00

AC:

AN:

36010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25092

East Asian (EAS)

AF:

0.00

AC:

AN:

35912

South Asian (SAS)

AF:

0.00

AC:

AN:

79590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5070

European-Non Finnish (NFE)

AF:

0.00000648

AC:

AN:

1080486

Other (OTH)

AF:

0.00

AC:

AN:

57864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.38

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.2

PhyloP100

0.37

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.5

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.51

MutPred

0.44

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.78

MPC

0.11

ClinPred

0.75

GERP RS

3.5

Varity_R

0.097

gMVP

0.64

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over