rs529406351
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005419.4(STAT2):c.1326G>A(p.Leu442=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,614,220 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00037 ( 10 hom. )
Consequence
STAT2
NM_005419.4 synonymous
NM_005419.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.57
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 12-56349441-C-T is Benign according to our data. Variant chr12-56349441-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.57 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000236 (36/152326) while in subpopulation SAS AF= 0.00748 (36/4814). AF 95% confidence interval is 0.00555. There are 1 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT2 | NM_005419.4 | c.1326G>A | p.Leu442= | synonymous_variant | 15/24 | ENST00000314128.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT2 | ENST00000314128.9 | c.1326G>A | p.Leu442= | synonymous_variant | 15/24 | 1 | NM_005419.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152208Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000728 AC: 183AN: 251492Hom.: 3 AF XY: 0.00103 AC XY: 140AN XY: 135920
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GnomAD4 exome AF: 0.000371 AC: 542AN: 1461894Hom.: 10 Cov.: 32 AF XY: 0.000536 AC XY: 390AN XY: 727248
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GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152326Hom.: 1 Cov.: 31 AF XY: 0.000389 AC XY: 29AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 02, 2024 | - - |
STAT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at