12-103638064-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_017564.10(STAB2):c.758C>T(p.Thr253Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,614,172 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (3 hom.)
• Consequence: STAB2 NM_017564.10 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.520

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01598993).
• BP6: Variant 12-103638064-C-T is Benign according to our data. Variant chr12-103638064-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 714544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAB2	NM_017564.10	c.758C>T	p.Thr253Met	missense_variant	8/69	ENST00000388887.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAB2	ENST00000388887.7	c.758C>T	p.Thr253Met	missense_variant	8/69	1	NM_017564.10	P1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000461 AC: 116 AN: 251410 Hom.: 0 AF XY: 0.000258 AC XY: 35 AN XY: 135872

Gnomad AFR exome AF: 0.00652

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000189 AC: 276 AN: 1461878 Hom.: 3 Cov.: 31 AF XY: 0.000140 AC XY: 102 AN XY: 727238

Gnomad4 AFR exome AF: 0.00654

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74478

Gnomad4 AFR AF: 0.00712

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00219

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000651 AC: 79

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	STAB2: BP4 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.034	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.58
MVP		0.46
MPC		0.43
ClinPred		0.058	T
GERP RS		3.4
Varity_R		0.056
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs74580351; hg19: chr12-104031842;