rs2228685

Positions:

• chr16-83032360-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.366+142T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 650,656 control chromosomes in the GnomAD database, including 96,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22360 hom., cov: 32)
  • Exomes 𝑓: 0.54 (73840 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-83032360-T-A is Benign according to our data. Variant chr16-83032360-T-A is described in ClinVar as [Benign]. Clinvar id is 1244376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.366+142T>A		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.366+142T>A		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82177 AN: 151900 Hom.: 22327 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.539 AC: 268799 AN: 498638 Hom.: 73840 Cov.: 6 AF XY: 0.540 AC XY: 139641 AN XY: 258644

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.541 AC: 82273 AN: 152018 Hom.: 22360 Cov.: 32 AF XY: 0.545 AC XY: 40493 AN XY: 74274

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.520

Alfa AF: 0.541 Hom.: 2754

Bravo AF: 0.530

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.90
CADD	Benign	1.6
DANN	Benign	0.73

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: rs2228685; hg19: chr16-83065965; COSMIC: COSV51817135; COSMIC: COSV51817135;