16-64947363-G-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001797.4(CDH11):c.*239_*240insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,017,050 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1 hom.)
• Consequence: CDH11 NM_001797.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.403

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH11	NM_001797.4	c.*239_*240insA		3_prime_UTR_variant	13/13	ENST00000268603.9
CDH11	NM_001308392.2	c.*727_*728insA		3_prime_UTR_variant	14/14
CDH11	NM_001330576.2	c.*239_*240insA		3_prime_UTR_variant	12/12
CDH11	XM_047433486.1	c.*239_*240insA		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.*239_*240insA		3_prime_UTR_variant	13/13	1	NM_001797.4	P1
CDH11	ENST00000394156.7	c.*727_*728insA		3_prime_UTR_variant	14/14	1

Frequencies

GnomAD3 genomes AF: 0.000196 AC: 29 AN: 147978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000105

Gnomad OTH AF: 0.000492

GnomAD4 exome AF: 0.0269 AC: 23355 AN: 868988 Hom.: 1 Cov.: 27 AF XY: 0.0272 AC XY: 11209 AN XY: 412572

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.0557

Gnomad4 ASJ exome AF: 0.0406

Gnomad4 EAS exome AF: 0.0530

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.0521

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0318

GnomAD4 genome AF: 0.000203 AC: 30 AN: 148062 Hom.: 0 Cov.: 32 AF XY: 0.000166 AC XY: 12 AN XY: 72152

Gnomad4 AFR AF: 0.000272

Gnomad4 AMR AF: 0.000269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000792

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.000207

Gnomad4 NFE AF: 0.000105

Gnomad4 OTH AF: 0.000487

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Orofacial cleft 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Grupo de Genetica Humana, Facultad de Medicina - Universidad de La Sabana

Nov 22, 2022

VUS in a strongly conserved region in the CDH11 gene, which encodes a member of a superfamily of cadherins. A dysregulation of these type of cadherins is thought to be involved in Elsahy-Waters Syndrome, which sometimes presents with craniofacial clefts, including cleft palate, as well as in Teebi hypertelorism syndrome. -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34181449; hg19: chr16-64981266;