rs41269593

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003730.6(RNASET2):c.643G>A(p.Glu215Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,614,092 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 26 hom. )

Consequence

RNASET2
NM_003730.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.589

Publications

12 publications found

Variant links:

Genes affected

RNASET2 (HGNC:21686): (ribonuclease T2) This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]

RNASET2 Gene-Disease associations (from GenCC):

cystic leukoencephalopathy without megalencephaly
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Illumina, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

RNASET2 links:

ENSG00000249141 (HGNC:):

ENSG00000249141 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003730.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005907774).

BP6

Variant 6-166929716-C-T is Benign according to our data. Variant chr6-166929716-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00437 (666/152238) while in subpopulation AMR AF = 0.0072 (110/15284). AF 95% confidence interval is 0.00611. There are 1 homozygotes in GnomAd4. There are 317 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003730.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASET2	NM_003730.6	MANE Select	c.643G>A	p.Glu215Lys	missense	Exon 9 of 9	NP_003721.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNASET2	ENST00000508775.6	TSL:1 MANE Select	c.643G>A	p.Glu215Lys	missense	Exon 9 of 9	ENSP00000426455.2	O00584-1
ENSG00000249141	ENST00000507747.1	TSL:5	c.432+4375G>A		intron	N/A	ENSP00000426906.1	H0YAE9
RNASET2	ENST00000870284.1		c.781G>A	p.Glu261Lys	missense	Exon 10 of 10	ENSP00000540343.1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00721

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00598

Gnomad OTH

AF:

0.00719

GnomAD2 exomes

AF:

0.00437

AC:

1098

AN:

251406

AF XY:

0.00411

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00622

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00528

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.00539

AC:

7881

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

3774

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33478

American (AMR)

AF:

0.00662

AC:

296

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

359

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00264

AC:

141

AN:

53392

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00603

AC:

6709

AN:

1112004

Other (OTH)

AF:

0.00522

AC:

315

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

466

933

1399

1866

2332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00437

AC:

666

AN:

152238

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41556

American (AMR)

AF:

0.00720

AC:

110

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00598

AC:

407

AN:

68016

Other (OTH)

AF:

0.00712

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00524

Hom.:

Bravo

AF:

0.00458

EpiCase

AF:

0.00616

EpiControl

AF:

0.00486

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Cystic leukoencephalopathy without megalencephaly (1)

RNASET2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.010

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.82

M_CAP

Benign

0.039

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

PhyloP100

0.59

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

REVEL

Benign

0.23

Sift

Benign

0.19

Sift4G

Uncertain

0.027

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.098

gMVP

0.46

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over