Genetic Variant RNASEH2B:p.Asp9Asn (chr13-50910101-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024570.4(RNASEH2B):c.25G>A(p.Asp9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D9V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

RNASEH2B
NM_024570.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Publications

0 publications found

Variant links:

Genes affected

RNASEH2B (HGNC:25671): (ribonuclease H2 subunit B) RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]

RNASEH2B links:

RNASEH2B-AS1 (HGNC:39967): (RNASEH2B antisense RNA 1)

RNASEH2B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21254602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNASEH2B	NM_024570.4	MANE Select	c.25G>A	p.Asp9Asn	missense	Exon 1 of 11	NP_078846.2	Q5TBB1-1
RNASEH2B	NM_001411023.1		c.25G>A	p.Asp9Asn	missense	Exon 1 of 11	NP_001397952.1	A0A2R8Y883
RNASEH2B	NM_001142279.2		c.25G>A	p.Asp9Asn	missense	Exon 1 of 10	NP_001135751.1	Q5TBB1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNASEH2B	ENST00000336617.8	TSL:1 MANE Select	c.25G>A	p.Asp9Asn	missense	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
RNASEH2B	ENST00000646960.1		c.25G>A	p.Asp9Asn	missense	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8
RNASEH2B	ENST00000642721.1		c.25G>A	p.Asp9Asn	missense	Exon 1 of 12	ENSP00000495650.1	A0A2R8Y6Y1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.63e-7

AC:

AN:

1310940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

644836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26078

American (AMR)

AF:

0.00

AC:

AN:

22790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22216

East Asian (EAS)

AF:

0.00

AC:

AN:

28230

South Asian (SAS)

AF:

0.00

AC:

AN:

69436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4110

European-Non Finnish (NFE)

AF:

9.59e-7

AC:

AN:

1042518

Other (OTH)

AF:

0.00

AC:

AN:

54060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aicardi-Goutieres syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00071

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.21

MetaSVM

Uncertain

0.11

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.50

REVEL

Benign

0.17

Sift

Benign

0.055

Sift4G

Benign

0.42

Polyphen

0.20

Vest4

0.15

MutPred

0.39

Gain of catalytic residue at V11 (P = 0)

MVP

0.71

MPC

0.048

ClinPred

0.48

GERP RS

2.8

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.11

gMVP

0.15

Mutation Taster

=94/6

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over