2-6892487-T-C

Position:

• chr2-6892487-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382040.4(RSAD2):​c.889-1184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,082 control chromosomes in the GnomAD database, including 33,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33058 hom., cov: 32)
• Consequence: RSAD2 ENST00000382040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD2	NM_080657.5	c.889-1184T>C		intron_variant		ENST00000382040.4	NP_542388.2
RSAD2	NM_001410702.1	c.685-1184T>C		intron_variant			NP_001397631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD2	ENST00000382040.4	c.889-1184T>C		intron_variant		1	NM_080657.5	ENSP00000371471	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98347 AN: 151964 Hom.: 33043 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.647 AC: 98391 AN: 152082 Hom.: 33058 Cov.: 32 AF XY: 0.651 AC XY: 48413 AN XY: 74334

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.657

Alfa AF: 0.708 Hom.: 78940

Bravo AF: 0.637

Asia WGS AF: 0.675 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.70

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: rs16865717; hg19: chr2-7032618;