dbSNP rs7306642: STAB2:p.Pro2039Thr (chr12-103745256-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017564.10(STAB2):c.6115C>A(p.Pro2039Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,613,284 control chromosomes in the GnomAD database, including 4,346 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.099 ( 982 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3364 hom. )

Consequence

STAB2
NM_017564.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

STAB2 (HGNC:18629): (stabilin 2) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 15 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to bind and endocytose ligands such as hyaluronan, low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein has been shown to cycle between the plasma membrane and lysosomes. [provided by RefSeq, Jul 2008]

STAB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002451688).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAB2	NM_017564.10 link	c.6115C>A	p.Pro2039Thr	missense_variant	Exon 57 of 69	ENST00000388887.7	NP_060034.9	Q8WWQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7 link	c.6115C>A	p.Pro2039Thr	missense_variant	Exon 57 of 69	1	NM_017564.10	ENSP00000373539.2		Q8WWQ8

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15087

AN:

152024

Hom.:

982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0419

Gnomad AMR

AF:

0.0751

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0337

Gnomad FIN

AF:

0.0800

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0957

GnomAD3 exomes

AF:

0.0657

AC:

16426

AN:

249974

Hom.:

731

AF XY:

0.0619

AC XY:

8363

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0356

Gnomad FIN exome

AF:

0.0769

Gnomad NFE exome

AF:

0.0638

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0635

AC:

92788

AN:

1461142

Hom.:

3364

Cov.:

AF XY:

0.0626

AC XY:

45504

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.0579

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0748

Gnomad4 NFE exome

AF:

0.0627

Gnomad4 OTH exome

AF:

0.0675

GnomAD4 genome

AF:

0.0993

AC:

15106

AN:

152142

Hom.:

982

Cov.:

AF XY:

0.0974

AC XY:

7242

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0750

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0336

Gnomad4 FIN

AF:

0.0800

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.0952

Alfa

AF:

0.0717

Hom.:

1181

Bravo

AF:

0.102

TwinsUK

AF:

0.0647

AC:

240

ALSPAC

AF:

0.0553

AC:

213

ESP6500AA

AF:

0.188

AC:

830

ESP6500EA

AF:

0.0653

AC:

562

ExAC

AF:

0.0668

AC:

8108

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0664

EpiControl

AF:

0.0672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.15

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.3

REVEL

Benign

0.062

Sift

Benign

0.28

Sift4G

Uncertain

0.055

Polyphen

0.016

Vest4

0.037

MPC

0.092

ClinPred

0.014

GERP RS

3.4

Varity_R

0.092

gMVP

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over