chr16-83032059-G-C

Variant names:

• chr16-83032059-G-C
• rs6565105
• NM_001257.5:c.207G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. 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. Synonymous variant affecting the same amino acid position (i.e. S69S) has been classified as Benign.

• 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
• Publications: 25 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.166 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.207G>C	p.Ser69Ser	synonymous	Exon 3 of 14	NP_001248.1
	CDH13	NM_001220488.2		c.348G>C	p.Ser116Ser	synonymous	Exon 4 of 15	NP_001207417.1
	CDH13	NM_001220489.2		c.207G>C	p.Ser69Ser	synonymous	Exon 3 of 13	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.207G>C	p.Ser69Ser	synonymous	Exon 3 of 14	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.207G>C	p.Ser69Ser	synonymous	Exon 3 of 5	ENSP00000408632.3
	CDH13	ENST00000268613.14	TSL:2	c.348G>C	p.Ser116Ser	synonymous	Exon 4 of 15	ENSP00000268613.10

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

GnomAD2 exomes AF: 0.000826 AC: 198 AN: 239634 AF XY: 0.000810

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 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

African (AFR) AF: 0.000120 AC: 4 AN: 33414

American (AMR) AF: 0.000137 AC: 6 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25998

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39420

South Asian (SAS) AF: 0.000660 AC: 56 AN: 84874

European-Finnish (FIN) AF: 0.000546 AC: 29 AN: 53104

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.00171 AC: 1902 AN: 1109332

Other (OTH) AF: 0.00179 AC: 108 AN: 60192

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

African (AFR) AF: 0.000337 AC: 14 AN: 41482

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 67988

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000438 Hom.: 49023

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		-0.17
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs6565105; hg19: chr16-83065664;