rs1555514463

Positions:

• chr16-64982183-GAG-GCTGATGATC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001797.4(CDH11):​c.1116_1117delinsGATCATCAG​(p.Ile372MetfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDH11 NM_001797.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P: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]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-64982184-AG-CTGATGATC is Pathogenic according to our data. Variant chr16-64982184-AG-CTGATGATC is described in ClinVar as [Pathogenic]. Clinvar id is 523098.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4	c.1116_1117delinsGATCATCAG	p.Ile372MetfsTer9	frameshift_variant	8/13	ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.1116_1117delinsGATCATCAG	p.Ile372MetfsTer9	frameshift_variant	8/14		NP_001295321.1
CDH11	NM_001330576.2	c.738_739delinsGATCATCAG	p.Ile246MetfsTer9	frameshift_variant	7/12		NP_001317505.1
CDH11	XM_047433486.1	c.738_739delinsGATCATCAG	p.Ile246MetfsTer9	frameshift_variant	7/12		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9	c.1116_1117delinsGATCATCAG	p.Ile372MetfsTer9	frameshift_variant	8/13	1	NM_001797.4	ENSP00000268603	P1
CDH11	ENST00000394156.7	c.1116_1117delinsGATCATCAG	p.Ile372MetfsTer9	frameshift_variant	8/14	1		ENSP00000377711
	ENST00000624875.1	n.1043_1044delinsGATCATCAG		non_coding_transcript_exon_variant	1/1
CDH11	ENST00000566827.5	c.738_739delinsGATCATCAG	p.Ile246MetfsTer9	frameshift_variant	7/12	2		ENSP00000457812

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Elsahy-Waters syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555514463; hg19: chr16-65016087;