rs6822297

chr4-26999373-A-Gchr4-26999373-A-T

Variant summary

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

The NM_020860.4(STIM2):c.625+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,417,130 control chromosomes in the GnomAD database, including 142,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11538 hom., cov: 31)
  • Exomes 𝑓: 0.45 (131348 hom.)
• Consequence: STIM2 NM_020860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

Genes affected

STIM2 (HGNC:19205): (stromal interaction molecule 2) This gene is a member of the stromal interaction molecule (STIM) family and likely arose, along with related family member STIM1, from a common ancestral gene. The encoded protein functions to regulate calcium concentrations in the cytosol and endoplasmic reticulum, and is involved in the activation of plasma membrane Orai Ca(2+) entry channels. This gene initiates translation from a non-AUG (UUG) start site. A signal peptide is cleaved from the resulting protein. Multiple transcript variants result from alternative splicing. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM2	NM_020860.4	c.625+26A>G		intron_variant		ENST00000467087.7
STIM2	NM_001169117.2	c.625+26A>G		intron_variant
STIM2	NM_001169118.2	c.625+26A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM2	ENST00000467087.7	c.625+26A>G		intron_variant		1	NM_020860.4	P2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55736 AN: 151790 Hom.: 11535 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.418 AC: 91503 AN: 218690 Hom.: 20141 AF XY: 0.425 AC XY: 50567 AN XY: 119088

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.397

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.448 AC: 566783 AN: 1265222 Hom.: 131348 Cov.: 15 AF XY: 0.447 AC XY: 284490 AN XY: 637106

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.367 AC: 55754 AN: 151908 Hom.: 11538 Cov.: 31 AF XY: 0.367 AC XY: 27273 AN XY: 74266

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.386

Alfa AF: 0.446 Hom.: 27015

Bravo AF: 0.352

Asia WGS AF: 0.265 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.36
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6822297; hg19: chr4-27000995; COSMIC: COSV52837345; COSMIC: COSV52837345;