16-64947363-GTT-GTTTTT

Variant names:

• chr16-64947363-G-GTTT
• rs34181449
• NM_001797.4:c.*237_*239dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001797.4(CDH11):​c.*237_*239dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 1,000,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CDH11 NM_001797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*237_*239dupAAA		3_prime_UTR	Exon 13 of 13	NP_001788.2
	CDH11	NM_001308392.2		c.*725_*727dupAAA		3_prime_UTR	Exon 14 of 14	NP_001295321.1	P55287-2
	CDH11	NM_001330576.2		c.*237_*239dupAAA		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.*237_*239dupAAA		3_prime_UTR	Exon 13 of 13	ENSP00000268603.4	P55287-1
	CDH11	ENST00000394156.7	TSL:1	c.*725_*727dupAAA		3_prime_UTR	Exon 14 of 14	ENSP00000377711.3	P55287-2
	CDH11	ENST00000871590.1		c.*237_*239dupAAA		splice_region	Exon 4 of 4	ENSP00000541649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000300 AC: 3 AN: 1000550 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 474988

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22654

American (AMR) AF: 0.00 AC: 0 AN: 9992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13326

East Asian (EAS) AF: 0.0000426 AC: 1 AN: 23450

South Asian (SAS) AF: 0.0000312 AC: 1 AN: 32012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2566

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840906

Other (OTH) AF: 0.00 AC: 0 AN: 40122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34181449; hg19: chr16-64981266;