12-103631668-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017564.10(STAB2):c.558G>A(p.Ala186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,614,164 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (48 hom.)
• Consequence: STAB2 NM_017564.10 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.04

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-103631668-G-A is Benign according to our data. Variant chr12-103631668-G-A is described in ClinVar as [Benign]. Clinvar id is 775099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.04 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAB2	NM_017564.10	c.558G>A	p.Ala186=	synonymous_variant	6/69	ENST00000388887.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAB2	ENST00000388887.7	c.558G>A	p.Ala186=	synonymous_variant	6/69	1	NM_017564.10	P1

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 796 AN: 152182 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00875

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00629 AC: 1581 AN: 251410 Hom.: 9 AF XY: 0.00643 AC XY: 873 AN XY: 135872

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00448

Gnomad FIN exome AF: 0.00901

Gnomad NFE exome AF: 0.00931

Gnomad OTH exome AF: 0.00700

GnomAD4 exome AF: 0.00766 AC: 11198 AN: 1461864 Hom.: 48 Cov.: 31 AF XY: 0.00758 AC XY: 5509 AN XY: 727232

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00486

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.00860

Gnomad4 OTH exome AF: 0.00687

GnomAD4 genome AF: 0.00523 AC: 796 AN: 152300 Hom.: 2 Cov.: 32 AF XY: 0.00459 AC XY: 342 AN XY: 74472

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.00875

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00775 Hom.: 1

Bravo AF: 0.00509

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00960

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.86
Dann	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs147053330; hg19: chr12-104025446;