Variant 16-64948660-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308392.2(CDH11):c.2022A>G(p.Ile674Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDH11
NM_001308392.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

CDH11 (HGNC:1750): (cadherin 11) 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. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. [provided by RefSeq, Jul 2008]

CDH11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15111095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4 linkuse as main transcript	c.1895-561A>G		intron_variant		ENST00000268603.9	NP_001788.2	P55287-1
CDH11	NM_001308392.2 linkuse as main transcript	c.2022A>G	p.Ile674Met	missense_variant	13/14		NP_001295321.1	P55287-2
CDH11	NM_001330576.2 linkuse as main transcript	c.1517-561A>G		intron_variant			NP_001317505.1	H3BUU9
CDH11	XM_047433486.1 linkuse as main transcript	c.1517-561A>G		intron_variant			XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDH11	ENST00000394156.7 linkuse as main transcript	c.2022A>G	p.Ile674Met	missense_variant	13/14	1		ENSP00000377711.3	P55287-2
CDH11	ENST00000268603.9 linkuse as main transcript	c.1895-561A>G		intron_variant		1	NM_001797.4	ENSP00000268603.4	P55287-1
CDH11	ENST00000566827.5 linkuse as main transcript	c.1517-561A>G		intron_variant		2		ENSP00000457812.1	H3BUU9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238584

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131084

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459360

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725932

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000865

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

CDH11: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.4

DANN

Benign

0.52

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.23

M_CAP

Benign

0.027

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.90

PROVEAN

Benign

0.70

REVEL

Benign

0.041

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Polyphen

0.78

Vest4

0.20

MutPred

0.52

Loss of catalytic residue at L679 (P = 0.0225);

MVP

0.48

ClinPred

0.095

GERP RS

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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