chr16-64947363-G-GTT

Variant names:

• chr16-64947363-G-GTT
• rs34181449
• NM_001797.4:c.*238_*239dupAA

Variant summary

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

The NM_001797.4(CDH11):​c.*238_*239dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,147,582 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: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*238_*239dupAA		3_prime_UTR	Exon 13 of 13	NP_001788.2
	CDH11	NM_001308392.2		c.*726_*727dupAA		3_prime_UTR	Exon 14 of 14	NP_001295321.1	P55287-2
	CDH11	NM_001330576.2		c.*238_*239dupAA		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.*238_*239dupAA		3_prime_UTR	Exon 13 of 13	ENSP00000268603.4	P55287-1
	CDH11	ENST00000394156.7	TSL:1	c.*726_*727dupAA		3_prime_UTR	Exon 14 of 14	ENSP00000377711.3	P55287-2
	CDH11	ENST00000871590.1		c.*238_*239dupAA		splice_region	Exon 4 of 4	ENSP00000541649.1

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000560 AC: 56 AN: 999532 Hom.: 0 Cov.: 27 AF XY: 0.0000717 AC XY: 34 AN XY: 474484

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

African (AFR) AF: 0.0000442 AC: 1 AN: 22616

American (AMR) AF: 0.000200 AC: 2 AN: 9978

Ashkenazi Jewish (ASJ) AF: 0.0000752 AC: 1 AN: 13304

East Asian (EAS) AF: 0.000128 AC: 3 AN: 23412

South Asian (SAS) AF: 0.000282 AC: 9 AN: 31968

European-Finnish (FIN) AF: 0.000194 AC: 3 AN: 15494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2564

European-Non Finnish (NFE) AF: 0.0000429 AC: 36 AN: 840116

Other (OTH) AF: 0.0000250 AC: 1 AN: 40080

⚠️ 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 AF: 0.00000675 AC: 1 AN: 148050 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72098

African (AFR) AF: 0.00 AC: 0 AN: 40320

American (AMR) AF: 0.00 AC: 0 AN: 14846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 4686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66792

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 5

Bravo AF: 0.00000378

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;