11-44618303-G-T

Variant names:

• chr11-44618303-G-T
• rs200920132
• NM_002231.4:c.580G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002231.4(CD82):​c.580G>T​(p.Glu194*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,638 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD82 NM_002231.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002231.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD82	NM_002231.4	MANE Select	c.580G>T	p.Glu194*	stop_gained	Exon 8 of 10	NP_002222.1	P27701-1
	CD82	NM_001024844.2		c.505G>T	p.Glu169*	stop_gained	Exon 7 of 9	NP_001020015.1	P27701-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD82	ENST00000227155.9	TSL:1 MANE Select	c.580G>T	p.Glu194*	stop_gained	Exon 8 of 10	ENSP00000227155.4	P27701-1
	CD82	ENST00000878578.1		c.721G>T	p.Glu241*	stop_gained	Exon 8 of 10	ENSP00000548637.1
	CD82	ENST00000878563.1		c.580G>T	p.Glu194*	stop_gained	Exon 8 of 10	ENSP00000548622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Benign	0.94
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.050	N
PhyloP100		-2.3
Vest4		0.90
GERP RS		-4.3
PromoterAI		0.0038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=48/152	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -19

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

Other links and lift over

dbSNP: rs200920132; hg19: chr11-44639853;