Genetic Variant NM_005534.4:c.788C>T (chr21-33432780-C-T) – 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_005534.4(IFNGR2):c.788C>T(p.Ala263Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

IFNGR2
NM_005534.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.203

Publications

0 publications found

Variant links:

Genes affected

IFNGR2 (HGNC:5440): (interferon gamma receptor 2) This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. [provided by RefSeq, Jul 2008]

IFNGR2 links:

TMEM50B (HGNC:1280): (transmembrane protein 50B) Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM50B 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=0.13434252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005534.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFNGR2	NM_005534.4	MANE Select	c.788C>T	p.Ala263Val	missense	Exon 6 of 7	NP_005525.2
IFNGR2	NM_001329128.2		c.845C>T	p.Ala282Val	missense	Exon 7 of 8	NP_001316057.1	E7EUY1
TMEM50B	NR_040016.2		n.2798G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.788C>T	p.Ala263Val	missense	Exon 6 of 7	ENSP00000290219.5	P38484
TMEM50B	ENST00000420455.5	TSL:1	n.*2143G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000397773.1	P56557
TMEM50B	ENST00000420455.5	TSL:1	n.*2143G>A		3_prime_UTR	Exon 9 of 9	ENSP00000397773.1	P56557

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.059

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.71

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.20

PrimateAI

Benign

0.27

PROVEAN

Benign

0.50

REVEL

Benign

0.035

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.029

Vest4

0.068

MutPred

0.42

Gain of helix (P = 0.132)

MVP

0.75

MPC

0.41

ClinPred

0.071

GERP RS

0.86

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.25

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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