rs6822297

Variant names:

• chr4-26999373-A-G
• rs6822297
• NM_020860.4:c.625+26A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-26999373-A-G
• chr4-26999373-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020860.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM2	NM_020860.4	MANE Select	c.625+26A>G		intron	N/A	NP_065911.3
	STIM2	NM_001169118.2		c.625+26A>G		intron	N/A	NP_001162589.1	H0Y860
	STIM2	NM_001169117.2		c.625+26A>G		intron	N/A	NP_001162588.1	Q9P246-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM2	ENST00000467087.7	TSL:1 MANE Select	c.625+26A>G		intron	N/A	ENSP00000419073.2	Q9P246-1
	STIM2	ENST00000465503.6	TSL:1	c.625+26A>G		intron	N/A	ENSP00000417569.2	H0Y860
	STIM2	ENST00000467011.6	TSL:1	c.625+26A>G		intron	N/A	ENSP00000419383.2	Q9P246-3

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

GnomAD2 exomes AF: 0.418 AC: 91503 AN: 218690 AF XY: 0.425

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 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

African (AFR) AF: 0.170 AC: 4740 AN: 27960

American (AMR) AF: 0.399 AC: 14935 AN: 37458

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 10721 AN: 23674

East Asian (EAS) AF: 0.148 AC: 5339 AN: 36000

South Asian (SAS) AF: 0.391 AC: 29847 AN: 76266

European-Finnish (FIN) AF: 0.489 AC: 25178 AN: 51470

Middle Eastern (MID) AF: 0.402 AC: 2137 AN: 5318

European-Non Finnish (NFE) AF: 0.473 AC: 451550 AN: 954154

Other (OTH) AF: 0.422 AC: 22336 AN: 52922

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

African (AFR) AF: 0.180 AC: 7438 AN: 41432

American (AMR) AF: 0.364 AC: 5559 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1531 AN: 3464

East Asian (EAS) AF: 0.165 AC: 850 AN: 5158

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4820

European-Finnish (FIN) AF: 0.489 AC: 5148 AN: 10528

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31909 AN: 67940

Other (OTH) AF: 0.386 AC: 814 AN: 2110

Alfa AF: 0.430 Hom.: 43032

Bravo AF: 0.352

Asia WGS AF: 0.265 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.36
DANN	Benign	0.62
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs6822297; hg19: chr4-27000995; COSMIC: COSV52837345; COSMIC: COSV52837345;