rs749820676

Variant names:

• chr11-44618307-C-A
• rs749820676
• NM_002231.4:c.584C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-44618307-C-A
• chr11-44618307-C-G
• chr11-44618307-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002231.4(CD82):​c.584C>A​(p.Ala195Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A195V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CD82 NM_002231.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09327373).

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.584C>A	p.Ala195Asp	missense	Exon 8 of 10	NP_002222.1	P27701-1
	CD82	NM_001024844.2		c.509C>A	p.Ala170Asp	missense	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.584C>A	p.Ala195Asp	missense	Exon 8 of 10	ENSP00000227155.4	P27701-1
	CD82	ENST00000878578.1		c.725C>A	p.Ala242Asp	missense	Exon 8 of 10	ENSP00000548637.1
	CD82	ENST00000878563.1		c.584C>A	p.Ala195Asp	missense	Exon 8 of 10	ENSP00000548622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461578 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33470

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: 53146

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.023
DANN	Benign	0.77
DEOGEN2	Benign	0.37	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-3.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.054
Sift	Benign	0.55	T
Sift4G	Benign	0.56	T
Polyphen		0.0040	B
Vest4		0.32
MutPred		0.45		Gain of solvent accessibility (P = 0.0354)
MVP		0.49
MPC		0.32
ClinPred		0.078	T
GERP RS		0.030
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.67
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs749820676; hg19: chr11-44639857;