16-82858053-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001257.5(CDH13):c.46-309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 152,278 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (482 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 16-82858053-A-G is Benign according to our data. Variant chr16-82858053-A-G is described in ClinVar as [Benign]. Clinvar id is 1277753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.46-309A>G		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.46-309A>G		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10677 AN: 152160 Hom.: 483 Cov.: 33

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0701 AC: 10672 AN: 152278 Hom.: 482 Cov.: 33 AF XY: 0.0703 AC XY: 5236 AN XY: 74458

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0889 Hom.: 520

Bravo AF: 0.0646

Asia WGS AF: 0.0520 AC: 179 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	19
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs17740866; hg19: chr16-82891658;