chr16-83032059-G-C

Position:

• chr16-83032059-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001257.5(CDH13):​c.207G>C​(p.Ser69Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,608,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: CDH13 NM_001257.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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]

CDH13 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.166 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.207G>C	p.Ser69Ser	synonymous_variant	3/14	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.207G>C	p.Ser69Ser	synonymous_variant	3/14	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.000783 AC: 119 AN: 151962 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000826 AC: 198 AN: 239634 Hom.: 0 AF XY: 0.000810 AC XY: 105 AN XY: 129648

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.000209

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.000173

Gnomad SAS exome AF: 0.000584

Gnomad FIN exome AF: 0.000760

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00145 AC: 2110 AN: 1455974 Hom.: 1 Cov.: 49 AF XY: 0.00142 AC XY: 1029 AN XY: 723628

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000137

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000660

Gnomad4 FIN exome AF: 0.000546

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.000789 AC: 120 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.000579 AC XY: 43 AN XY: 74306

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.0000621 Hom.: 34220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.2
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;