rs41285577

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_StrongBA1

The NM_017838.4(NHP2):c.160+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,782 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 42 hom., cov: 33)

Exomes 𝑓: 0.014 ( 264 hom. )

Consequence

NHP2
NM_017838.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.30

Publications

2 publications found

Variant links:

Genes affected

NHP2 (HGNC:14377): (NHP2 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nhp2p. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

NHP2 Gene-Disease associations (from GenCC):

dyskeratosis congenita, autosomal recessive 2
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
dyskeratosis congenita
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NHP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-178153642-C-G is Benign according to our data. Variant chr5-178153642-C-G is described in ClinVar as Benign. ClinVar VariationId is 260941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017838.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NHP2	NM_017838.4	MANE Select	c.160+16G>C	intron	N/A	NP_060308.1	Q9NX24
NHP2	NM_001396110.1		c.160+16G>C	intron	N/A	NP_001383039.1
NHP2	NM_001034833.2		c.160+16G>C	intron	N/A	NP_001030005.1	J3QSY4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NHP2	ENST00000274606.8	TSL:1 MANE Select	c.160+16G>C	intron	N/A	ENSP00000274606.4	Q9NX24
NHP2	ENST00000510363.1	TSL:1	n.227+16G>C	intron	N/A
NHP2	ENST00000940843.1		c.160+16G>C	intron	N/A	ENSP00000610902.1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2594

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.0859

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.00705

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0172

AC:

4306

AN:

249626

AF XY:

0.0163

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.00981

Gnomad ASJ exome

AF:

0.00768

Gnomad EAS exome

AF:

0.0922

Gnomad FIN exome

AF:

0.00657

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0137

AC:

20036

AN:

1461432

Hom.:

264

Cov.:

AF XY:

0.0134

AC XY:

9742

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0223

AC:

748

AN:

33474

American (AMR)

AF:

0.0112

AC:

501

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00767

AC:

200

AN:

26092

East Asian (EAS)

AF:

0.0770

AC:

3057

AN:

39690

South Asian (SAS)

AF:

0.00676

AC:

583

AN:

86218

European-Finnish (FIN)

AF:

0.00699

AC:

373

AN:

53362

Middle Eastern (MID)

AF:

0.0251

AC:

145

AN:

5766

European-Non Finnish (NFE)

AF:

0.0121

AC:

13416

AN:

1111774

Other (OTH)

AF:

0.0168

AC:

1013

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1218

2436

3653

4871

6089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.0170

AC:

2595

AN:

152350

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1248

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0213

AC:

884

AN:

41586

American (AMR)

AF:

0.0166

AC:

254

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00606

AC:

AN:

3468

East Asian (EAS)

AF:

0.0859

AC:

445

AN:

5180

South Asian (SAS)

AF:

0.00890

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00705

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

823

AN:

68032

Other (OTH)

AF:

0.0194

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00587

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dyskeratosis congenita (1)

Dyskeratosis congenita, autosomal recessive 2 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.37

PhyloP100

-1.3

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.5

Mutation Taster

=100/0

polymorphism (auto)

(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

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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