12-56349443-G-A

Variant names:

• chr12-56349443-G-A
• NM_005419.4:c.1324C>T
• STAT2 p.Leu442Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005419.4(STAT2):​c.1324C>T​(p.Leu442Leu) variant causes a synonymous change. 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. Synonymous variant affecting the same amino acid position (i.e. L442L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STAT2 NM_005419.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• Publications: 0 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• pseudo-TORCH syndrome 3

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

ACMG classification

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 (BayesDel_noAF=-0.28).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT2	NM_005419.4	MANE Select	c.1324C>T	p.Leu442Leu	synonymous	Exon 15 of 24	NP_005410.1	P52630-3
	STAT2	NM_198332.2		c.1312C>T	p.Leu438Leu	synonymous	Exon 15 of 24	NP_938146.1	P52630-4
	STAT2	NM_001385114.1		c.1303C>T	p.Leu435Leu	synonymous	Exon 14 of 23	NP_001372043.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT2	ENST00000314128.9	TSL:1 MANE Select	c.1324C>T	p.Leu442Leu	synonymous	Exon 15 of 24	ENSP00000315768.4	P52630-3
	STAT2	ENST00000556539.5	TSL:1	n.254C>T		non_coding_transcript_exon	Exon 2 of 11
	STAT2	ENST00000922389.1		c.1324C>T	p.Leu442Leu	synonymous	Exon 15 of 24	ENSP00000592448.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	9.6
DANN	Benign	0.86
PhyloP100		4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56743227;