chr4-26999373-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020860.4(STIM2):​c.625+26A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIM2	NM_020860.4	c.625+26A>T		intron_variant	Intron 5 of 11	ENST00000467087.7	NP_065911.3
STIM2	NM_001169118.2	c.625+26A>T		intron_variant	Intron 5 of 12		NP_001162589.1
STIM2	NM_001169117.2	c.625+26A>T		intron_variant	Intron 5 of 12		NP_001162588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIM2	ENST00000467087.7	c.625+26A>T		intron_variant	Intron 5 of 11	1	NM_020860.4	ENSP00000419073.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1268644 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 638788

African (AFR) AF: 0.00 AC: 0 AN: 27998

American (AMR) AF: 0.00 AC: 0 AN: 37520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23742

East Asian (EAS) AF: 0.00 AC: 0 AN: 36022

South Asian (SAS) AF: 0.00 AC: 0 AN: 76478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 956936

Other (OTH) AF: 0.00 AC: 0 AN: 53060

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 43032

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;