12-103654676-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017564.10(STAB2):c.1529C>G(p.Pro510Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000601 in 1,613,874 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P510H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (6 hom.)
• Consequence: STAB2 NM_017564.10 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.41

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04344678).
• BP6: Variant 12-103654676-C-G is Benign according to our data. Variant chr12-103654676-C-G is described in ClinVar as [Benign]. Clinvar id is 747239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAB2	NM_017564.10	c.1529C>G	p.Pro510Arg	missense_variant	13/69	ENST00000388887.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAB2	ENST00000388887.7	c.1529C>G	p.Pro510Arg	missense_variant	13/69	1	NM_017564.10	P1

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 517 AN: 152136 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000868 AC: 218 AN: 251072 Hom.: 5 AF XY: 0.000523 AC XY: 71 AN XY: 135698

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000306 AC: 447 AN: 1461620 Hom.: 6 Cov.: 31 AF XY: 0.000250 AC XY: 182 AN XY: 727092

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.000761

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.00344 AC: 523 AN: 152254 Hom.: 4 Cov.: 32 AF XY: 0.00337 AC XY: 251 AN XY: 74452

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00000628 Hom.: 1209

Bravo AF: 0.00393

ExAC AF: 0.00107 AC: 130

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.043	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.4	M
MutationTaster	Benign	0.00039	P
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.44
Sift	Benign	0.031	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.79
MPC		0.45
ClinPred		0.11	T
GERP RS		5.8
Varity_R		0.38
gMVP		0.67

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

Other links and lift over

dbSNP: rs1609860; hg19: chr12-104048454;