16-64948602-G-C

Position:

• chr16-64948602-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_001308392.2(CDH11):​c.2073+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000896 in 1,607,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (1 hom.)
• Consequence: CDH11 NM_001308392.2 splice_region, intron
• Scores: Splicing: ADA: 0.00006552
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.746

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-64948602-G-C is Benign according to our data. Variant chr16-64948602-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033576.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000407 (62/152274) while in subpopulation AFR AF= 0.00144 (60/41548). AF 95% confidence interval is 0.00115. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4	c.1895-503C>G		intron_variant		ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.2073+7C>G		splice_region_variant, intron_variant			NP_001295321.1
CDH11	NM_001330576.2	c.1517-503C>G		intron_variant			NP_001317505.1
CDH11	XM_047433486.1	c.1517-503C>G		intron_variant			XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9	c.1895-503C>G		intron_variant		1	NM_001797.4	ENSP00000268603.4
CDH11	ENST00000394156.7	c.2073+7C>G		splice_region_variant, intron_variant		1		ENSP00000377711.3
CDH11	ENST00000566827.5	c.1517-503C>G		intron_variant		2		ENSP00000457812.1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000112 AC: 27 AN: 240548 Hom.: 0 AF XY: 0.0000832 AC XY: 11 AN XY: 132138

Gnomad AFR exome AF: 0.00189

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000564 AC: 82 AN: 1454930 Hom.: 1 Cov.: 30 AF XY: 0.0000470 AC XY: 34 AN XY: 724170

Gnomad4 AFR exome AF: 0.00216

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.0000498

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74466

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000563

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CDH11-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.24
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

Publications

LitVar

Other links and lift over

dbSNP: rs571457064; hg19: chr16-64982505;