16-82639464-A-G

Variant names:

• chr16-82639464-A-G
• rs150875489
• NM_001257.5:c.45+12327A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001220488.2(CDH13):​c.185A>G​(p.Gln62Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000735 in 1,530,588 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (5 hom.)
• Consequence: CDH13 NM_001220488.2 missense, splice_region
• Scores: Splicing: ADA: 0.0001302
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.563

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005779505).
• BP6: Variant 16-82639464-A-G is Benign according to our data. Variant chr16-82639464-A-G is described in ClinVar as [Benign]. Clinvar id is 3048874.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+12327A>G		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.45+12327A>G		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.00373 AC: 568 AN: 152204 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000896 AC: 115 AN: 128370 AF XY: 0.000839

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.000616

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000251

GnomAD4 exome AF: 0.000403 AC: 556 AN: 1378266 Hom.: 5 Cov.: 27 AF XY: 0.000344 AC XY: 234 AN XY: 680448

Gnomad4 AFR exome AF: 0.0125 AC: 393 AN: 31522

Gnomad4 AMR exome AF: 0.000560 AC: 20 AN: 35688

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25152

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35700

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 79126

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 33464

Gnomad4 NFE exome AF: 0.0000801 AC: 86 AN: 1074178

Gnomad4 Remaining exome AF: 0.000935 AC: 54 AN: 57752

GnomAD4 genome AF: 0.00374 AC: 569 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.00340 AC XY: 253 AN XY: 74492

Gnomad4 AFR AF: 0.0129 AC: 0.0128939 AN: 0.0128939

Gnomad4 AMR AF: 0.000980 AC: 0.000980136 AN: 0.000980136

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.00014699 AN: 0.00014699

Gnomad4 OTH AF: 0.00378 AC: 0.0037843 AN: 0.0037843

Alfa AF: 0.00582 Hom.: 1

Bravo AF: 0.00420

ExAC AF: 0.000356 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CDH13-related disorder Benign:1

Jun 05, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.54
DANN	Benign	0.85
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.016
Sift	Benign	0.044	D
Sift4G	Benign	0.061	T
Vest4		0.077
MVP		0.49
MPC		0.10
ClinPred		0.00098	T
GERP RS		-2.0
gMVP		0.31
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.64		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150875489; hg19: chr16-82673069;