16-64947765-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_001797.4(CDH11):c.2229C>T(p.Tyr743=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,614,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: CDH11 NM_001797.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 16-64947765-G-A is Benign according to our data. Variant chr16-64947765-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000604 (92/152210) while in subpopulation AMR AF= 0.00163 (25/15294). AF 95% confidence interval is 0.00114. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH11	NM_001797.4	c.2229C>T	p.Tyr743=	synonymous_variant	13/13	ENST00000268603.9
CDH11	NM_001330576.2	c.1851C>T	p.Tyr617=	synonymous_variant	12/12
CDH11	XM_047433486.1	c.1851C>T	p.Tyr617=	synonymous_variant	12/12
CDH11	NM_001308392.2	c.*326C>T		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.2229C>T	p.Tyr743=	synonymous_variant	13/13	1	NM_001797.4	P1
CDH11	ENST00000394156.7	c.*326C>T		3_prime_UTR_variant	14/14	1
CDH11	ENST00000566827.5	c.1851C>T	p.Tyr617=	synonymous_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000919 AC: 231 AN: 251384 Hom.: 1 AF XY: 0.000883 AC XY: 120 AN XY: 135866

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000473 AC: 691 AN: 1461882 Hom.: 1 Cov.: 33 AF XY: 0.000474 AC XY: 345 AN XY: 727242

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000310

Gnomad4 OTH exome AF: 0.000546

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74408

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000442 Hom.: 0

Bravo AF: 0.000771

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CDH11: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	8.0
Dann	Benign	0.43

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: rs145843219; hg19: chr16-64981668; COSMIC: COSV51762075;