Variant 5-26885688-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016279.4(CDH9):c.1808A>G(p.Glu603Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,613,688 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 78 hom. )

Consequence

CDH9
NM_016279.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.98

Variant links:

Genes affected

CDH9 (HGNC:1768): (cadherin 9) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. [provided by RefSeq, Jul 2008]

CDH9 links:

CDH9 (HGNC:):

CDH9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0105982125).

BP6

Variant 5-26885688-T-C is Benign according to our data. Variant chr5-26885688-T-C is described in ClinVar as [Benign]. Clinvar id is 770716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 893 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH9	NM_016279.4 linkuse as main transcript	c.1808A>G	p.Glu603Gly	missense_variant	11/12	ENST00000231021.9	NP_057363.3	Q9ULB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH9	ENST00000231021.9 linkuse as main transcript	c.1808A>G	p.Glu603Gly	missense_variant	11/12	1	NM_016279.4	ENSP00000231021.4		Q9ULB4
CDH9	ENST00000505020.1 linkuse as main transcript	n.824A>G		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

893

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00937

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00881

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00668

AC:

1673

AN:

250618

Hom.:

AF XY:

0.00753

AC XY:

1020

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00550

Gnomad ASJ exome

AF:

0.00497

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00820

Gnomad OTH exome

AF:

0.00818

GnomAD4 exome

AF:

0.00704

AC:

10292

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

5296

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00238

Gnomad4 NFE exome

AF:

0.00749

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00587

AC:

893

AN:

152226

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00936

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00881

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00798

Hom.:

Bravo

AF:

0.00587

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00677

AC:

822

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.31

Sift

Benign

0.045

Sift4G

Benign

0.16

Polyphen

0.38

Vest4

0.74

MVP

0.49

MPC

0.60

ClinPred

0.061

GERP RS

5.9

Varity_R

0.33

gMVP

0.72

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