rs2228685

Variant names:

• chr16-83032360-T-A
• rs2228685
• NM_001257.5:c.366+142T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.366+142T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 650,656 control chromosomes in the GnomAD database, including 96,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22360 hom., cov: 32)
  • Exomes 𝑓: 0.54 (73840 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-83032360-T-A is Benign according to our data. Variant chr16-83032360-T-A is described in ClinVar as [Benign]. Clinvar id is 1244376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.366+142T>A		intron_variant	Intron 3 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.366+142T>A		intron_variant	Intron 3 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82177 AN: 151900 Hom.: 22327 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.539 AC: 268799 AN: 498638 Hom.: 73840 Cov.: 6 AF XY: 0.540 AC XY: 139641 AN XY: 258644

African (AFR) AF: 0.524 AC: 6982 AN: 13330

American (AMR) AF: 0.537 AC: 10119 AN: 18848

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 6207 AN: 13974

East Asian (EAS) AF: 0.448 AC: 13945 AN: 31146

South Asian (SAS) AF: 0.578 AC: 25172 AN: 43516

European-Finnish (FIN) AF: 0.624 AC: 20274 AN: 32490

Middle Eastern (MID) AF: 0.466 AC: 1309 AN: 2812

European-Non Finnish (NFE) AF: 0.540 AC: 170069 AN: 314898

Other (OTH) AF: 0.533 AC: 14722 AN: 27624

GnomAD4 genome AF: 0.541 AC: 82273 AN: 152018 Hom.: 22360 Cov.: 32 AF XY: 0.545 AC XY: 40493 AN XY: 74274

African (AFR) AF: 0.524 AC: 21735 AN: 41450

American (AMR) AF: 0.539 AC: 8233 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2320 AN: 5160

South Asian (SAS) AF: 0.577 AC: 2773 AN: 4808

European-Finnish (FIN) AF: 0.636 AC: 6721 AN: 10560

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37130 AN: 67982

Other (OTH) AF: 0.520 AC: 1099 AN: 2112

Alfa AF: 0.541 Hom.: 2754

Bravo AF: 0.530

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.069
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: rs2228685; hg19: chr16-83065965; COSMIC: COSV51817135; COSMIC: COSV51817135;