Genetic Variant NM_005419.4:c.2478G>C (chr12-56343467-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005419.4(STAT2):c.2478G>C(p.Gln826His) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

STAT2
NM_005419.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

0 publications found

Variant links:

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)

STAT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12945357).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAT2	NM_005419.4	MANE Select	c.2478G>C	p.Gln826His	missense	Exon 24 of 24	NP_005410.1
STAT2	NM_198332.2		c.2466G>C	p.Gln822His	missense	Exon 24 of 24	NP_938146.1
STAT2	NM_001385114.1		c.2457G>C	p.Gln819His	missense	Exon 23 of 23	NP_001372043.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAT2	ENST00000314128.9	TSL:1 MANE Select	c.2478G>C	p.Gln826His	missense	Exon 24 of 24	ENSP00000315768.4
STAT2	ENST00000556539.5	TSL:1	n.1408G>C		non_coding_transcript_exon	Exon 11 of 11
STAT2	ENST00000557235.5	TSL:2	c.2466G>C	p.Gln822His	missense	Exon 24 of 24	ENSP00000450751.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.66

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PhyloP100

0.34

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.78

REVEL

Benign

0.083

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0030

Polyphen

0.0060

Vest4

0.14

MutPred

0.14

Gain of catalytic residue at N827 (P = 0.051)

MVP

0.35

MPC

0.40

ClinPred

0.093

GERP RS

3.5

Varity_R

0.14

gMVP

0.24

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over