Variant 11-44600218-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002231.4(CD82):c.124A>G(p.Ile42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CD82
NM_002231.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12460205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD82	NM_002231.4 linkuse as main transcript	c.124A>G	p.Ile42Val	missense_variant	4/10	ENST00000227155.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD82	ENST00000227155.9 linkuse as main transcript	c.124A>G	p.Ile42Val	missense_variant	4/10	1	NM_002231.4	P1	P27701-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251382

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000693

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000906

AC:

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 17, 2021

The c.124A>G (p.I42V) alteration is located in exon 4 (coding exon 2) of the CD82 gene. This alteration results from a A to G substitution at nucleotide position 124, causing the isoleucine (I) at amino acid position 42 to be replaced by a valine (V). 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

Benign

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.034

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

T;T;T;T;T;T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.71

N;N;N;N;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.096

T;T;T;T;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T;T;T;T

Polyphen

0.36

.;B;.;.;.;.;.;.

Vest4

0.30, 0.30

MVP

0.81

MPC

0.20

ClinPred

0.083

GERP RS

4.2

Varity_R

0.14

gMVP

0.25

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

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

Other links and lift over