Variant 12-103631642-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017564.10(STAB2):c.532G>A(p.Asp178Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,172 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 12 hom. )

Consequence

STAB2
NM_017564.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.785

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009839028).

BP6

Variant 12-103631642-G-A is Benign according to our data. Variant chr12-103631642-G-A is described in ClinVar as [Benign]. Clinvar id is 787928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00707 (1077/152288) while in subpopulation AFR AF= 0.0245 (1016/41542). AF 95% confidence interval is 0.0232. There are 13 homozygotes in gnomad4. There are 483 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAB2	NM_017564.10 linkuse as main transcript	c.532G>A	p.Asp178Asn	missense_variant	6/69	ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7 linkuse as main transcript	c.532G>A	p.Asp178Asn	missense_variant	6/69	1	NM_017564.10	ENSP00000373539	P1

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

1075

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00174

AC:

437

AN:

251470

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000685

AC:

1002

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000612

AC XY:

445

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00707

AC:

1077

AN:

152288

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00766

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

247

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Uncertain

0.0080

Polyphen

0.55

Vest4

0.37

MVP

0.71

MPC

0.078

ClinPred

0.027

GERP RS

0.49

Varity_R

0.087

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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