chr16-82858432-A-G

Position:

• chr16-82858432-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.116A>G​(p.Asn39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,613,538 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (53 hom., cov: 33)
  • Exomes 𝑓: 0.014 (479 hom.)
• Consequence: CDH13 NM_001257.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.55

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023998022).
• BP6: Variant 16-82858432-A-G is Benign according to our data. Variant chr16-82858432-A-G is described in ClinVar as [Benign]. Clinvar id is 257648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.116A>G	p.Asn39Ser	missense_variant	2/14	ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.116A>G	p.Asn39Ser	missense_variant	2/14	1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2895 AN: 152222 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00886

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0214 AC: 5328 AN: 249040 Hom.: 181 AF XY: 0.0240 AC XY: 3247 AN XY: 135094

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.0532

Gnomad SAS exome AF: 0.0810

Gnomad FIN exome AF: 0.00548

Gnomad NFE exome AF: 0.00870

Gnomad OTH exome AF: 0.0151

GnomAD4 exome AF: 0.0137 AC: 19985 AN: 1461196 Hom.: 479 Cov.: 30 AF XY: 0.0156 AC XY: 11364 AN XY: 726908

Gnomad4 AFR exome AF: 0.0356

Gnomad4 AMR exome AF: 0.00438

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.0374

Gnomad4 SAS exome AF: 0.0772

Gnomad4 FIN exome AF: 0.00590

Gnomad4 NFE exome AF: 0.00814

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0190 AC: 2900 AN: 152342 Hom.: 53 Cov.: 33 AF XY: 0.0205 AC XY: 1526 AN XY: 74494

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0484

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.00886

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0113 Hom.: 34

Bravo AF: 0.0180

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.0312 AC: 118

ESP6500EA AF: 0.00742 AC: 61

ExAC AF: 0.0224 AC: 2710

Asia WGS AF: 0.0640 AC: 222 AN: 3478

EpiCase AF: 0.00873

EpiControl AF: 0.00705

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2021

This variant is associated with the following publications: (PMID: 27238071, 25450229) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.59
DEOGEN2	Benign	0.048	T;.;.;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.75	T;T;T;T;T;T
MetaRNN	Benign	0.0024	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.060	.;N;N;N;N;D
REVEL	Benign	0.11
Sift	Benign	0.78	.;T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;.
Vest4		0.18
MPC		0.059
ClinPred		0.00015	T
GERP RS		3.6
Varity_R		0.034
gMVP		0.098

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

Publications

LitVar

Other links and lift over

dbSNP: rs72807847; hg19: chr16-82892037; COSMIC: COSV51857354;