dbSNP rs376798752: NRDE2:p.Asp1083His (chr14-90286404-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017970.4(NRDE2):c.3247G>C(p.Asp1083His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1083N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NRDE2
NM_017970.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.58

Publications

0 publications found

Variant links:

Genes affected

NRDE2 (HGNC:20186): (NRDE-2, necessary for RNA interference, domain containing) Involved in several processes, including RNA splicing; negative regulation of RNA catabolic process; and positive regulation of RNA export from nucleus. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NRDE2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31380048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017970.4. 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
	NRDE2	NM_017970.4	MANE Select	c.3247G>C	p.Asp1083His	missense	Exon 12 of 14	NP_060440.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRDE2	ENST00000354366.8	TSL:1 MANE Select	c.3247G>C	p.Asp1083His	missense	Exon 12 of 14	ENSP00000346335.3	Q9H7Z3
NRDE2	ENST00000553409.5	TSL:1	n.*2772G>C		non_coding_transcript_exon	Exon 10 of 12	ENSP00000451025.1	G3V338
NRDE2	ENST00000556189.5	TSL:1	n.*1725G>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000452107.1	H0YJT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

M_CAP

Benign

0.059

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.3

PhyloP100

5.6

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.24

Sift

Benign

0.032

Sift4G

Uncertain

0.014

Polyphen

0.85

Vest4

0.39

MutPred

0.41

Gain of catalytic residue at R1081 (P = 8e-04)

MVP

0.79

MPC

0.10

ClinPred

0.97

GERP RS

5.6

Varity_R

0.20

gMVP

0.33

Mutation Taster

=61/39

polymorphism

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over