16-64947612-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.2382C>T(p.Asp794=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,604,778 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 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: CDH11 NM_001797.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.147

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=-0.53).
• BP6: Variant 16-64947612-G-A is Benign according to our data. Variant chr16-64947612-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.147 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000788 (12/152194) while in subpopulation SAS AF= 0.000831 (4/4816). AF 95% confidence interval is 0.000283. There are 0 homozygotes in gnomad4. There are 7 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.2382C>T	p.Asp794=	synonymous_variant	13/13	ENST00000268603.9
CDH11	NM_001330576.2	c.2004C>T	p.Asp668=	synonymous_variant	12/12
CDH11	XM_047433486.1	c.2004C>T	p.Asp668=	synonymous_variant	12/12
CDH11	NM_001308392.2	c.*479C>T		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.2382C>T	p.Asp794=	synonymous_variant	13/13	1	NM_001797.4	P1
CDH11	ENST00000394156.7	c.*479C>T		3_prime_UTR_variant	14/14	1
CDH11	ENST00000566827.5	c.2004C>T	p.Asp668=	synonymous_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000100 AC: 25 AN: 249806 Hom.: 0 AF XY: 0.0000814 AC XY: 11 AN XY: 135068

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000878

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 245 AN: 1452584 Hom.: 1 Cov.: 32 AF XY: 0.000172 AC XY: 124 AN XY: 720820

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000905

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.000279

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000167

Gnomad4 OTH exome AF: 0.000100

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74396

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000945

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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

Mar 01, 2023

CDH11: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	6.3
Dann	Benign	0.57

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: rs377222713; hg19: chr16-64981515; COSMIC: COSV51751843;