Variant 5-24488026-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006727.5(CDH10):c.2004G>C(p.Gln668His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CDH10
NM_006727.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

CDH10 (HGNC:1749): (cadherin 10) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and 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 histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is predominantly expressed in brain and is putatively involved in synaptic adhesions, axon outgrowth and guidance. Mutations in this gene may be associated with lung squamous cell carcinoma and colorectal cancer in human patients. [provided by RefSeq, Nov 2015]

CDH10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH10	NM_006727.5 linkuse as main transcript	c.2004G>C	p.Gln668His	missense_variant	12/12	ENST00000264463.8	NP_006718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDH10	ENST00000264463.8 linkuse as main transcript	c.2004G>C	p.Gln668His	missense_variant	12/12	1	NM_006727.5	ENSP00000264463	P1
CDH10	ENST00000510477.5 linkuse as main transcript	c.*556G>C		3_prime_UTR_variant, NMD_transcript_variant	11/11	1		ENSP00000425653
CDH10	ENST00000502921.5 linkuse as main transcript	n.795G>C		non_coding_transcript_exon_variant	5/5	3
CDH10	ENST00000503958.1 linkuse as main transcript	n.527G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.2004G>C (p.Q668H) alteration is located in exon 12 (coding exon 11) of the CDH10 gene. This alteration results from a G to C substitution at nucleotide position 2004, causing the glutamine (Q) at amino acid position 668 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.076

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.46

Sift

Uncertain

0.027

Sift4G

Uncertain

0.034

Polyphen

0.46

Vest4

0.59

MutPred

0.53

Gain of sheet (P = 0.0016);

MVP

0.77

MPC

1.3

ClinPred

0.97

GERP RS

3.7

Varity_R

0.33

gMVP

0.86

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