Genetic Variant CDH11:c.999+516G>T (chr16-64987641-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001797.4(CDH11):c.999+516G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,014 control chromosomes in the GnomAD database, including 6,023 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 6019 hom., cov: 32)

Exomes 𝑓: 0.29 ( 4 hom. )

Consequence

CDH11
NM_001797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Elsahy-Waters syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
Teebi hypertelorism syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CDH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CDH11	NM_001797.4 link	c.999+516G>T	intron_variant	Intron 7 of 12	ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2 link	c.999+516G>T	intron_variant	Intron 7 of 13		NP_001295321.1
CDH11	NM_001330576.2 link	c.621+516G>T	intron_variant	Intron 6 of 11		NP_001317505.1
CDH11	XM_047433486.1 link	c.621+516G>T	intron_variant	Intron 6 of 11		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CDH11	ENST00000268603.9 link	c.999+516G>T	intron_variant	Intron 7 of 12	1	NM_001797.4	ENSP00000268603.4
CDH11	ENST00000394156.7 link	c.999+516G>T	intron_variant	Intron 7 of 13	1		ENSP00000377711.3
CDH11	ENST00000619158.1 link	c.*507G>T	3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000484650.1
CDH11	ENST00000566827.5 link	c.621+516G>T	intron_variant	Intron 6 of 11	2		ENSP00000457812.1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39902

AN:

151804

Hom.:

6015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.349

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.293

AC:

AN:

Hom.:

Cov.:

AF XY:

0.289

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.263

AC:

39919

AN:

151922

Hom.:

6019

Cov.:

AF XY:

0.256

AC XY:

19030

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.121

AC:

5004

AN:

41474

American (AMR)

AF:

0.265

AC:

4037

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1157

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1070

AN:

5140

South Asian (SAS)

AF:

0.207

AC:

997

AN:

4808

European-Finnish (FIN)

AF:

0.248

AC:

2610

AN:

10530

Middle Eastern (MID)

AF:

0.355

AC:

103

AN:

290

European-Non Finnish (NFE)

AF:

0.353

AC:

23982

AN:

67944

Other (OTH)

AF:

0.281

AC:

592

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1461

2923

4384

5846

7307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.286

Hom.:

1241

Bravo

AF:

0.258

Asia WGS

AF:

0.170

AC:

592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.79

(source)

DANN

Benign

0.18

PhyloP100

0.073

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over