chr16-83032059-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001257.5(CDH13):​c.207G>A​(p.Ser69Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 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, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -19 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 VariationId is 257649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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>A	p.Ser69Ser	synonymous	Exon 3 of 14	NP_001248.1
	CDH13	NM_001220488.2		c.348G>A	p.Ser116Ser	synonymous	Exon 4 of 15	NP_001207417.1
	CDH13	NM_001220489.2		c.207G>A	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>A	p.Ser69Ser	synonymous	Exon 3 of 14	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.207G>A	p.Ser69Ser	synonymous	Exon 3 of 5	ENSP00000408632.3
	CDH13	ENST00000268613.14	TSL:2	c.348G>A	p.Ser116Ser	synonymous	Exon 4 of 15	ENSP00000268613.10

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

GnomAD2 exomes AF: 0.542 AC: 129800 AN: 239634 AF XY: 0.544

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 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

African (AFR) AF: 0.538 AC: 17985 AN: 33402

American (AMR) AF: 0.530 AC: 23240 AN: 43846

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11508 AN: 25986

East Asian (EAS) AF: 0.435 AC: 17131 AN: 39408

South Asian (SAS) AF: 0.571 AC: 48464 AN: 84860

European-Finnish (FIN) AF: 0.627 AC: 33289 AN: 53086

Middle Eastern (MID) AF: 0.462 AC: 2657 AN: 5756

European-Non Finnish (NFE) AF: 0.545 AC: 604274 AN: 1109014

Other (OTH) AF: 0.533 AC: 32049 AN: 60178

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

African (AFR) AF: 0.541 AC: 22414 AN: 41464

American (AMR) AF: 0.534 AC: 8170 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2269 AN: 5130

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4818

European-Finnish (FIN) AF: 0.637 AC: 6737 AN: 10572

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36966 AN: 67980

Other (OTH) AF: 0.520 AC: 1098 AN: 2110

Alfa AF: 0.531 Hom.: 49023

Bravo AF: 0.533

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.89
PhyloP100		-0.17
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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