16-64947363-GTT-GT

Variant names:

• chr16-64947363-GT-G
• rs34181449
• NM_001797.4:c.*239delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001797.4(CDH11):​c.*239delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,147,584 control chromosomes in the GnomAD database, including 1,421 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.039 (122 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1299 hom.)
• Consequence: CDH11 NM_001797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

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.*239delA		3_prime_UTR	Exon 13 of 13	NP_001788.2
	CDH11	NM_001308392.2		c.*727delA		3_prime_UTR	Exon 14 of 14	NP_001295321.1	P55287-2
	CDH11	NM_001330576.2		c.*239delA		3_prime_UTR	Exon 12 of 12	NP_001317505.1	H3BUU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH11	ENST00000268603.9	TSL:1 MANE Select	c.*239delA		3_prime_UTR	Exon 13 of 13	ENSP00000268603.4	P55287-1
	CDH11	ENST00000394156.7	TSL:1	c.*727delA		3_prime_UTR	Exon 14 of 14	ENSP00000377711.3	P55287-2
	CDH11	ENST00000871590.1		c.*239delA		splice_region	Exon 4 of 4	ENSP00000541649.1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5759 AN: 148034 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0342

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.0196

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.0559 AC: 55870 AN: 999466 Hom.: 1299 Cov.: 27 AF XY: 0.0556 AC XY: 26381 AN XY: 474460

African (AFR) AF: 0.0204 AC: 462 AN: 22626

American (AMR) AF: 0.0278 AC: 277 AN: 9976

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 532 AN: 13300

East Asian (EAS) AF: 0.0109 AC: 255 AN: 23404

South Asian (SAS) AF: 0.0402 AC: 1285 AN: 31974

European-Finnish (FIN) AF: 0.0474 AC: 733 AN: 15462

Middle Eastern (MID) AF: 0.0433 AC: 111 AN: 2562

European-Non Finnish (NFE) AF: 0.0597 AC: 50151 AN: 840070

Other (OTH) AF: 0.0515 AC: 2064 AN: 40092

GnomAD4 genome AF: 0.0389 AC: 5759 AN: 148118 Hom.: 122 Cov.: 32 AF XY: 0.0384 AC XY: 2771 AN XY: 72184

African (AFR) AF: 0.0226 AC: 913 AN: 40418

American (AMR) AF: 0.0264 AC: 393 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 117 AN: 3420

East Asian (EAS) AF: 0.0162 AC: 82 AN: 5050

South Asian (SAS) AF: 0.0430 AC: 201 AN: 4672

European-Finnish (FIN) AF: 0.0470 AC: 455 AN: 9684

Middle Eastern (MID) AF: 0.0210 AC: 6 AN: 286

European-Non Finnish (NFE) AF: 0.0524 AC: 3500 AN: 66774

Other (OTH) AF: 0.0365 AC: 75 AN: 2052

Alfa AF: 0.0134 Hom.: 5

Bravo AF: 0.0354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40
Mutation Taster		=100/0	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: rs34181449; hg19: chr16-64981266;