NM_005419.4:c.*1183C>A

Variant names:

• chr12-56342206-G-T
• rs11575248
• NM_005419.4:c.*1183C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005419.4(STAT2):​c.*1183C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 151,284 control chromosomes in the GnomAD database, including 220 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 0.046 (220 hom., cov: 30)
  • Exomes 𝑓: 0.022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STAT2 NM_005419.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 11 publications found

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]

STAT2 Gene-Disease associations (from GenCC):

• primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• pseudo-TORCH syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005419.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT2	NM_005419.4	MANE Select	c.*1183C>A		3_prime_UTR	Exon 24 of 24	NP_005410.1
	STAT2	NM_198332.2		c.*1183C>A		3_prime_UTR	Exon 24 of 24	NP_938146.1
	STAT2	NM_001385114.1		c.*1183C>A		3_prime_UTR	Exon 23 of 23	NP_001372043.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT2	ENST00000314128.9	TSL:1 MANE Select	c.*1183C>A		3_prime_UTR	Exon 24 of 24	ENSP00000315768.4
	STAT2	ENST00000556539.5	TSL:1	n.2669C>A		non_coding_transcript_exon	Exon 11 of 11
	STAT2	ENST00000922389.1		c.*1183C>A		3_prime_UTR	Exon 24 of 24	ENSP00000592448.1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6899 AN: 151170 Hom.: 217 Cov.: 30

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0288

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0224 AC: 3 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.0288 AC XY: 3 AN XY: 104

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0263 AC: 3 AN: 114

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0457 AC: 6911 AN: 151284 Hom.: 220 Cov.: 30 AF XY: 0.0448 AC XY: 3304 AN XY: 73826

African (AFR) AF: 0.0108 AC: 446 AN: 41122

American (AMR) AF: 0.0533 AC: 808 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.0337 AC: 173 AN: 5134

South Asian (SAS) AF: 0.0194 AC: 93 AN: 4798

European-Finnish (FIN) AF: 0.0547 AC: 566 AN: 10350

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0682 AC: 4631 AN: 67928

Other (OTH) AF: 0.0333 AC: 70 AN: 2104

Alfa AF: 0.0592 Hom.: 43

Bravo AF: 0.0421

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.85
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11575248; hg19: chr12-56735990;