chr16-64947861-C-T

Variant names:

• chr16-64947861-C-T
• rs200766127
• NM_001797.4:c.2133G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001797.4(CDH11):​c.2133G>A​(p.Ala711Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,614,100 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: CDH11 NM_001797.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.34
• Publications: 3 publications found

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: G2P, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• Teebi hypertelorism syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-64947861-C-T is Benign according to our data. Variant chr16-64947861-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2646587.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.34 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00023 (35/152216) while in subpopulation SAS AF = 0.00353 (17/4820). AF 95% confidence interval is 0.00225. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH11	NM_001797.4	MANE Select	c.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 13	NP_001788.2
	CDH11	NM_001330576.2		c.1755G>A	p.Ala585Ala	synonymous	Exon 12 of 12	NP_001317505.1	H3BUU9
	CDH11	NM_001308392.2		c.*230G>A		3_prime_UTR	Exon 14 of 14	NP_001295321.1	P55287-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH11	ENST00000268603.9	TSL:1 MANE Select	c.2133G>A	p.Ala711Ala	synonymous	Exon 13 of 13	ENSP00000268603.4	P55287-1
	CDH11	ENST00000394156.7	TSL:1	c.*230G>A		3_prime_UTR	Exon 14 of 14	ENSP00000377711.3	P55287-2
	CDH11	ENST00000566827.5	TSL:2	c.1755G>A	p.Ala585Ala	synonymous	Exon 12 of 12	ENSP00000457812.1	H3BUU9

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000724 AC: 182 AN: 251450 AF XY: 0.000971

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000454 AC: 664 AN: 1461884 Hom.: 6 Cov.: 33 AF XY: 0.000595 AC XY: 433 AN XY: 727242

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00473 AC: 408 AN: 86258

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53420

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1112002

Other (OTH) AF: 0.000348 AC: 21 AN: 60396

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74416

African (AFR) AF: 0.0000241 AC: 1 AN: 41538

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000136

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.84
DANN	Benign	0.61
PhyloP100		-3.3
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs200766127; hg19: chr16-64981764; COSMIC: COSV51761611;