rs7306642

Positions:

• chr12-103745256-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.099 (982 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3364 hom.)
• Consequence: STAB2 NM_017564.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
STAB2	NM_017564.10	c.6115C>A	p.Pro2039Thr	missense_variant	57/69	ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.6115C>A	p.Pro2039Thr	missense_variant	57/69	1	NM_017564.10	ENSP00000373539.2

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15087 AN: 152024 Hom.: 982 Cov.: 32

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

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.: 31 AF XY: 0.0626 AC XY: 45504 AN XY: 726812

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.: 32 AF XY: 0.0974 AC XY: 7242 AN XY: 74384

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: 68 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	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.57
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.062
Sift	Benign	0.28	T
Sift4G	Uncertain	0.055	T
Polyphen		0.016	B
Vest4		0.037
MPC		0.092
ClinPred		0.014	T
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

Other links and lift over

dbSNP: rs7306642; hg19: chr12-104139034; COSMIC: COSV66339070; COSMIC: COSV66339070;