16-83032059-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001257.5(CDH13):c.207G>A(p.Ser69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,607,566 control chromosomes in the GnomAD database, including 238,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22572 hom., cov: 32)
  • Exomes 𝑓: 0.54 (215552 hom.)
• Consequence: CDH13 NM_001257.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 16-83032059-G-A is Benign according to our data. Variant chr16-83032059-G-A is described in ClinVar as [Benign]. Clinvar id is 257649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.166 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.207G>A	p.Ser69=	synonymous_variant	3/14	ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.207G>A	p.Ser69=	synonymous_variant	3/14	1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82560 AN: 151910 Hom.: 22539 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.516

GnomAD3 exomes AF: 0.542 AC: 129800 AN: 239634 Hom.: 35300 AF XY: 0.544 AC XY: 70479 AN XY: 129648

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.445

Gnomad SAS exome AF: 0.567

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.543 AC: 790597 AN: 1455536 Hom.: 215552 Cov.: 49 AF XY: 0.543 AC XY: 392860 AN XY: 723424

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.544 AC: 82658 AN: 152030 Hom.: 22572 Cov.: 32 AF XY: 0.548 AC XY: 40680 AN XY: 74280

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.520

Alfa AF: 0.528 Hom.: 34220

Bravo AF: 0.533

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	9.1
Dann	Benign	0.89

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: rs6565105; hg19: chr16-83065664; COSMIC: COSV51836002;