Variant 11-44594712-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002231.4(CD82):c.50A>G(p.Asn17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD82
NM_002231.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

CD82 (HGNC:6210): (CD82 molecule) This metastasis suppressor gene product is a membrane glycoprotein that is a member of the transmembrane 4 superfamily. Expression of this gene has been shown to be downregulated in tumor progression of human cancers and can be activated by p53 through a consensus binding sequence in the promoter. Its expression and that of p53 are strongly correlated, and the loss of expression of these two proteins is associated with poor survival for prostate cancer patients. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CD82 links:

CD82 (HGNC:):

CD82 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD82	NM_002231.4 linkuse as main transcript	c.50A>G	p.Asn17Ser	missense_variant	3/10	ENST00000227155.9	NP_002222.1	P27701-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD82	ENST00000227155.9 linkuse as main transcript	c.50A>G	p.Asn17Ser	missense_variant	3/10	1	NM_002231.4	ENSP00000227155.4		P27701-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461342

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.50A>G (p.N17S) alteration is located in exon 3 (coding exon 1) of the CD82 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the asparagine (N) at amino acid position 17 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

.;D;.;T;.;T;D;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.57

MutationAssessor

Pathogenic

3.0

.;M;M;.;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.019

D;D;D;D;.;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D;D;D;D

Polyphen

1.0

.;D;.;.;.;.;.;.

Vest4

0.69

MutPred

0.86

.;Gain of glycosylation at N17 (P = 0.2785);Gain of glycosylation at N17 (P = 0.2785);Gain of glycosylation at N17 (P = 0.2785);Gain of glycosylation at N17 (P = 0.2785);.;Gain of glycosylation at N17 (P = 0.2785);Gain of glycosylation at N17 (P = 0.2785);

MVP

0.96

MPC

0.71

ClinPred

1.0

GERP RS

4.8

Varity_R

0.86

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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