Variant 2-6883444-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_080657.5(RSAD2):c.420G>A(p.Val140Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,192 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 16 hom. )

Consequence

RSAD2
NM_080657.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.706

Variant links:

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]

RSAD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-6883444-G-A is Benign according to our data. Variant chr2-6883444-G-A is described in ClinVar as [Benign]. Clinvar id is 780335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00748 (1140/152312) while in subpopulation AFR AF= 0.0266 (1104/41550). AF 95% confidence interval is 0.0253. There are 18 homozygotes in gnomad4. There are 538 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD2	NM_080657.5 link	c.420G>A	p.Val140Val	synonymous_variant	2/6	ENST00000382040.4	NP_542388.2	Q8WXG1
RSAD2	NM_001410702.1 link	c.216G>A	p.Val72Val	synonymous_variant	2/6		NP_001397631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD2	ENST00000382040.4 link	c.420G>A	p.Val140Val	synonymous_variant	2/6	1	NM_080657.5	ENSP00000371471.3		Q8WXG1

Frequencies

GnomAD3 genomes

AF:

0.00747

AC:

1137

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00173

AC:

434

AN:

251450

Hom.:

AF XY:

0.00127

AC XY:

172

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000772

AC:

1129

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

469

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00748

AC:

1140

AN:

152312

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

538

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0266

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00800

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.37

Position offset: -3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over