rs7306642

Variant names:

• chr12-103745256-C-A
• rs7306642
• NM_017564.10:c.6115C>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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	c.6115C>A	p.Pro2039Thr	missense_variant	Exon 57 of 69	ENST00000388887.7	NP_060034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAB2	ENST00000388887.7	c.6115C>A	p.Pro2039Thr	missense_variant	Exon 57 of 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

GnomAD2 exomes AF: 0.0657 AC: 16426 AN: 249974 AF XY: 0.0619

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 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

African (AFR) AF: 0.185 AC: 6187 AN: 33466

American (AMR) AF: 0.0579 AC: 2588 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2972 AN: 26104

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39682

South Asian (SAS) AF: 0.0346 AC: 2980 AN: 86184

European-Finnish (FIN) AF: 0.0748 AC: 3975 AN: 53130

Middle Eastern (MID) AF: 0.0548 AC: 314 AN: 5726

European-Non Finnish (NFE) AF: 0.0627 AC: 69692 AN: 1111780

Other (OTH) AF: 0.0675 AC: 4074 AN: 60366

GnomAD4 genome AF: 0.0993 AC: 15106 AN: 152142 Hom.: 982 Cov.: 32 AF XY: 0.0974 AC XY: 7242 AN XY: 74384

African (AFR) AF: 0.187 AC: 7740 AN: 41490

American (AMR) AF: 0.0750 AC: 1146 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4826

European-Finnish (FIN) AF: 0.0800 AC: 847 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4574 AN: 68002

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0771 Hom.: 2014

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
PhyloP100		2.4
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
Mutation Taster		=99/1	polymorphism (auto)

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