rs1802585

chr21-33436893-C-AchrNW_003315970.2-31464-C-Achr21-33436893-C-TchrNW_003315970.2-31464-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005534.4(IFNGR2):c.945C>A(p.Asp315Glu) 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. 15/21 in silico tools predict 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. D315D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFNGR2 NM_005534.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.55

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07415512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR2	NM_005534.4	c.945C>A	p.Asp315Glu	missense_variant	7/7	ENST00000290219.11
IFNGR2	NM_001329128.2	c.1002C>A	p.Asp334Glu	missense_variant	8/8
TMEM50B	XM_011529746.3	c.*2220G>T		3_prime_UTR_variant	9/10
TMEM50B	NR_040016.2	n.2775+2321G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR2	ENST00000290219.11	c.945C>A	p.Asp315Glu	missense_variant	7/7	1	NM_005534.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	0.0020
Dann	Benign	0.97
DEOGEN2	Benign	0.074	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.95	P;P;.
Vest4		0.042
MutPred		0.20		.;Gain of catalytic residue at W336 (P = 0.0443);.;
MVP		0.79
MPC		0.78
ClinPred		0.23	T
GERP RS		-8.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs1802585; hg19: chr21-34809200;