rs2325934

Variant names:

• chr16-83308892-A-C
• rs2325934
• NM_001257.5:c.637-35970A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.637-35970A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,310 control chromosomes in the GnomAD database, including 527 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 0.070 (527 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 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.637-35970A>C		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.778-35970A>C		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.520-35970A>C		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.637-35970A>C		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.778-35970A>C		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.520-35970A>C		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10617 AN: 152192 Hom.: 526 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0697 AC: 10614 AN: 152310 Hom.: 527 Cov.: 33 AF XY: 0.0694 AC XY: 5171 AN XY: 74482

African (AFR) AF: 0.0170 AC: 709 AN: 41588

American (AMR) AF: 0.0567 AC: 868 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1254 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7177 AN: 68018

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0911 Hom.: 378

Bravo AF: 0.0622

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.47
PhyloP100		-0.59
Mutation Taster		=100/0	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: rs2325934; hg19: chr16-83342497;