2-6883376-G-C

Position:

• chr2-6883376-G-C

Variant summary

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

The NM_080657.5(RSAD2):​c.352G>C​(p.Glu118Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RSAD2 NM_080657.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34

Genes affected

RSAD2 (HGNC:30908): (radical S-adenosyl methionine domain containing 2) The protein encoded by this gene is an interferon-inducible antiviral protein that belongs to the S-adenosyl-L-methionine (SAM) superfamily of enzymes. The protein plays a role in cellular antiviral response and innate immune signaling. Antiviral effects result from inhibition of viral RNA replication, interference in the secretory pathway, binding to viral proteins and dysregulation of cellular lipid metabolism. The protein has been found to inhibit both DNA and RNA viruses, including influenza virus, human immunodeficiency virus (HIV-1) and Zika virus. [provided by RefSeq, Sep 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD2	NM_080657.5	c.352G>C	p.Glu118Gln	missense_variant	2/6	ENST00000382040.4	NP_542388.2
RSAD2	NM_001410702.1	c.148G>C	p.Glu50Gln	missense_variant	2/6		NP_001397631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD2	ENST00000382040.4	c.352G>C	p.Glu118Gln	missense_variant	2/6	1	NM_080657.5	ENSP00000371471.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.352G>C (p.E118Q) alteration is located in exon 2 (coding exon 2) of the RSAD2 gene. This alteration results from a G to C substitution at nucleotide position 352, causing the glutamic acid (E) at amino acid position 118 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	.;D
Vest4		0.71
MutPred		0.42		.;Loss of disorder (P = 0.094);
MVP		0.69
MPC		0.24
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-7023507;