rs2020854
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005419.4(STAT2):c.1257+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,613,970 control chromosomes in the GnomAD database, including 14,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.20 ( 6143 hom., cov: 31)
Exomes 𝑓: 0.076 ( 8386 hom. )
Consequence
STAT2
NM_005419.4 splice_donor_region, intron
NM_005419.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.000003225
2
Clinical Significance
Conservation
PhyloP100: -0.514
Genes affected
STAT2 (HGNC:11363): (signal transducer and activator of transcription 2) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 12-56349583-T-C is Benign according to our data. Variant chr12-56349583-T-C is described in ClinVar as [Benign]. Clinvar id is 1167213.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT2 | NM_005419.4 | c.1257+6A>G | splice_donor_region_variant, intron_variant | ENST00000314128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT2 | ENST00000314128.9 | c.1257+6A>G | splice_donor_region_variant, intron_variant | 1 | NM_005419.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.195 AC: 29663AN: 151962Hom.: 6111 Cov.: 31
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GnomAD3 exomes AF: 0.0894 AC: 22474AN: 251482Hom.: 2801 AF XY: 0.0785 AC XY: 10669AN XY: 135920
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GnomAD4 exome AF: 0.0757 AC: 110639AN: 1461890Hom.: 8386 Cov.: 33 AF XY: 0.0730 AC XY: 53104AN XY: 727248
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GnomAD4 genome AF: 0.196 AC: 29758AN: 152080Hom.: 6143 Cov.: 31 AF XY: 0.189 AC XY: 14049AN XY: 74344
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at